chr6-87473010-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_006416.5(SLC35A1):c.7G>T(p.Ala3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 682,164 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.013 ( 37 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 8 hom. )

Consequence

SLC35A1
NM_006416.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -0.137

Publications

2 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014354289).

BP6

Variant 6-87473010-G-T is Benign according to our data. Variant chr6-87473010-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 95393.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0125 (1910/152332) while in subpopulation AFR AF = 0.0423 (1759/41578). AF 95% confidence interval is 0.0407. There are 37 homozygotes in GnomAd4. There are 891 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A1	NM_006416.5 link	c.7G>T	p.Ala3Ser	missense_variant	Exon 1 of 8	ENST00000369552.9	NP_006407.1	P78382-1
SLC35A1	NM_001168398.2 link	c.7G>T	p.Ala3Ser	missense_variant	Exon 1 of 7		NP_001161870.1	P78382-2
LOC124901357	XR_007059668.1 link	n.-65C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35A1	ENST00000369552.9 link	c.7G>T	p.Ala3Ser	missense_variant	Exon 1 of 8	1	NM_006416.5	ENSP00000358565.4		P78382-1
ENSG00000213204	ENST00000507897.5 link	n.*61-4352G>T		intron_variant	Intron 13 of 15	2		ENSP00000426769.1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1898

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0421

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00811

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00364

AC:

AN:

15946

AF XY:

0.00222

show subpopulations

Gnomad AFR exome

AF:

0.0341

Gnomad AMR exome

AF:

0.00335

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00113

AC:

600

AN:

529832

Hom.:

Cov.:

AF XY:

0.000928

AC XY:

251

AN XY:

270430

show subpopulations

African (AFR)

AF:

0.0390

AC:

443

AN:

11352

American (AMR)

AF:

0.00410

AC:

AN:

8772

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12070

East Asian (EAS)

AF:

0.00

AC:

AN:

24536

South Asian (SAS)

AF:

0.0000977

AC:

AN:

30696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29780

Middle Eastern (MID)

AF:

0.000607

AC:

AN:

3294

European-Non Finnish (NFE)

AF:

0.0000444

AC:

AN:

383110

Other (OTH)

AF:

0.00378

AC:

AN:

26222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

110

137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0125

AC:

1910

AN:

152332

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

891

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0423

AC:

1759

AN:

41578

American (AMR)

AF:

0.00810

AC:

124

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68026

Other (OTH)

AF:

0.00851

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

172

259

345

431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00392

Hom.:

Bravo

AF:

0.0143

ESP6500AA

AF:

0.0317

AC:

127

ESP6500EA

AF:

0.000126

AC:

ExAC

AF:

0.00194

AC:

197

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Oct 11, 2016

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 06, 2017

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

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. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0050

.;T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.72

T;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.41

N;.;N

PhyloP100

-0.14

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.020

N;N;N

REVEL

Benign

0.060

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.46

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.14

MVP

0.22

MPC

0.31

ClinPred

0.0068

GERP RS

2.2

PromoterAI

-0.23

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.050

gMVP

0.22

Mutation Taster

=298/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over