6-87473010-G-T

Position:

chr6-87473010-G-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 95393.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Uncertain_significance=1}.

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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35A1	NM_006416.5 linkuse as main transcript	c.7G>T	p.Ala3Ser	missense_variant	1/8	ENST00000369552.9
SLC35A1	NM_001168398.2 linkuse as main transcript	c.7G>T	p.Ala3Ser	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35A1	ENST00000369552.9 linkuse as main transcript	c.7G>T	p.Ala3Ser	missense_variant	1/8	1	NM_006416.5	P1	P78382-1
SLC35A1	ENST00000369556.7 linkuse as main transcript	c.7G>T	p.Ala3Ser	missense_variant	1/7	1			P78382-2
SLC35A1	ENST00000369557.9 linkuse as main transcript	c.7G>T	p.Ala3Ser	missense_variant	1/6	2
SLC35A1	ENST00000464978.5 linkuse as main transcript	n.91+2297G>T		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes

AF:

0.00364

AC:

AN:

15946

Hom.:

AF XY:

0.00222

AC XY:

AN XY:

7662

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 SAS 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

Gnomad4 AFR exome

AF:

0.0390

Gnomad4 AMR exome

AF:

0.00410

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000977

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000444

Gnomad4 OTH exome

AF:

0.00378

GnomAD4 genome

AF:

0.0125

AC:

1910

AN:

152332

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

891

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0423

Gnomad4 AMR

AF:

0.00810

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0000974

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

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 06, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Oct 11, 2016	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 22, 2016

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

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

DANN

Benign

0.96

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

MutationTaster

Benign

1.0

D;N;N;N

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.050

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over