Genetic Variant SLC35A1:c.16+21G>A (chr6-87473040-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006416.5(SLC35A1):c.16+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000697 in 573,560 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

SLC35A1
NM_006416.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.101

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: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

SLC35A1 links:

ENSG00000213204 (HGNC:):

ENSG00000213204 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A1	NM_006416.5	MANE Select	c.16+21G>A		intron	N/A	NP_006407.1	P78382-1
	SLC35A1	NM_001168398.2		c.16+21G>A		intron	N/A	NP_001161870.1	P78382-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC35A1	ENST00000369552.9	TSL:1 MANE Select	c.16+21G>A	intron	N/A	ENSP00000358565.4	P78382-1
SLC35A1	ENST00000369556.7	TSL:1	c.16+21G>A	intron	N/A	ENSP00000358569.3	P78382-2
ENSG00000213204	ENST00000507897.5	TSL:2	n.*61-4322G>A	intron	N/A	ENSP00000426769.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000237

AC:

AN:

421362

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

215042

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9790

American (AMR)

AF:

0.00

AC:

AN:

8204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10880

East Asian (EAS)

AF:

0.00

AC:

AN:

23738

South Asian (SAS)

AF:

0.00

AC:

AN:

20374

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2944

European-Non Finnish (NFE)

AF:

0.00000342

AC:

AN:

292774

Other (OTH)

AF:

0.00

AC:

AN:

22154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.7

(source)

DANN

Benign

0.84

PhyloP100

0.10

PromoterAI

-0.054

Neutral

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over