NM_006416.5:c.19A>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006416.5(SLC35A1):c.19A>C(p.Asn7His) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00107 in 1,612,270 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 7 hom. )

Consequence

SLC35A1
NM_006416.5 missense, splice_region

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.98

Publications

0 publications found

Variant links:

Genes affected

SLC35A1 (HGNC:11021): (solute carrier family 35 member A1) The protein encoded by this gene is found in the membrane of the Golgi apparatus, where it transports nucleotide sugars into the Golgi. One such nucleotide sugar is CMP-sialic acid, which is imported into the Golgi by the encoded protein and subsequently glycosylated. Defects in this gene are a cause of congenital disorder of glycosylation type 2F (CDG2F). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2009]

SLC35A1 Gene-Disease associations (from GenCC):

SLC35A1-congenital disorder of glycosylation
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

SLC35A1 links:

ENSG00000213204 (HGNC:):

ENSG00000213204 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004863143).

BP6

Variant 6-87477364-A-C is Benign according to our data. Variant chr6-87477364-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00575 (876/152290) while in subpopulation AFR AF = 0.0195 (810/41542). AF 95% confidence interval is 0.0184. There are 2 homozygotes in GnomAd4. There are 403 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006416.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A1	NM_006416.5	MANE Select	c.19A>C	p.Asn7His	missense splice_region	Exon 2 of 8	NP_006407.1
	SLC35A1	NM_001168398.2		c.19A>C	p.Asn7His	missense splice_region	Exon 2 of 7	NP_001161870.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC35A1	ENST00000369552.9	TSL:1 MANE Select	c.19A>C	p.Asn7His	missense splice_region	Exon 2 of 8	ENSP00000358565.4
SLC35A1	ENST00000369556.7	TSL:1	c.19A>C	p.Asn7His	missense splice_region	Exon 2 of 7	ENSP00000358569.3
ENSG00000213204	ENST00000507897.5	TSL:2	n.*63A>C		splice_region non_coding_transcript_exon	Exon 14 of 16	ENSP00000426769.1

Frequencies

GnomAD3 genomes

AF:

0.00570

AC:

868

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00144

AC:

360

AN:

250156

AF XY:

0.00103

show subpopulations

Gnomad AFR exome

AF:

0.0196

Gnomad AMR exome

AF:

0.000897

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000586

AC:

855

AN:

1459980

Hom.:

Cov.:

AF XY:

0.000519

AC XY:

377

AN XY:

726368

show subpopulations

African (AFR)

AF:

0.0211

AC:

706

AN:

33464

American (AMR)

AF:

0.000961

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000928

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52102

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111532

Other (OTH)

AF:

0.00151

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

122

163

204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00575

AC:

876

AN:

152290

Hom.:

Cov.:

AF XY:

0.00541

AC XY:

403

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0195

AC:

810

AN:

41542

American (AMR)

AF:

0.00373

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68036

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

124

165

206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00211

Hom.:

Bravo

AF:

0.00670

ESP6500AA

AF:

0.0154

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00185

AC:

225

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 22, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Feb 06, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Oct 11, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

SLC35A1-congenital disorder of glycosylation

Benign:1

Dec 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC35A1-related disorder

Benign:1

Apr 06, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

5.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.6

REVEL

Benign

0.091

Sift

Uncertain

0.011

Sift4G

Uncertain

0.035

Polyphen

0.96

Vest4

0.39

MVP

0.63

MPC

0.68

ClinPred

0.027

GERP RS

5.6

Varity_R

0.14

gMVP

0.26

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over