9-96383480-T-C

Position:

chr9-96383480-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_007001.3(SLC35D2):c.155A>G(p.Tyr52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000966 in 1,490,938 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

SLC35D2
NM_007001.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38

Variant links:

Genes affected

SLC35D2 (HGNC:20799): (solute carrier family 35 member D2) Nucleotide sugars, which are synthesized in the cytosol or the nucleus, are high-energy donor substrates for glycosyltransferases located in the lumen of the endoplasmic reticulum and Golgi apparatus. Translocation of nucleotide sugars from the cytosol into the lumen compartment is mediated by specific nucleotide sugar transporters, such as SLC35D2 (Suda et al., 2004 [PubMed 15082721]).[supplied by OMIM, Mar 2008]

SLC35D2 links:

SLC35D2 (HGNC:):

SLC35D2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2647928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35D2	NM_007001.3 linkuse as main transcript	c.155A>G	p.Tyr52Cys	missense_variant	1/12	ENST00000253270.13	NP_008932.2	Q76EJ3-1A0A024R9N5
SLC35D2	NM_001286990.2 linkuse as main transcript	c.155A>G	p.Tyr52Cys	missense_variant	1/9		NP_001273919.1	Q76EJ3-2
SLC35D2	NR_104627.2 linkuse as main transcript	n.232A>G		non_coding_transcript_exon_variant	1/13
SLC35D2-HSD17B3	NR_182427.1 linkuse as main transcript	n.232A>G		non_coding_transcript_exon_variant	1/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC35D2	ENST00000253270.13 linkuse as main transcript	c.155A>G	p.Tyr52Cys	missense_variant	1/12	1	NM_007001.3	ENSP00000253270.7	Q76EJ3-1
SLC35D2	ENST00000375259.9 linkuse as main transcript	c.155A>G	p.Tyr52Cys	missense_variant	1/9	1		ENSP00000364408.4	Q76EJ3-2
SLC35D2	ENST00000375257.2 linkuse as main transcript	c.155A>G	p.Tyr52Cys	missense_variant	1/6	2		ENSP00000364406.1	Q5VZJ2
SLC35D2	ENST00000482643.2 linkuse as main transcript	n.201A>G		non_coding_transcript_exon_variant	1/9	5

Frequencies

GnomAD3 genomes

AF:

0.0000334

AC:

AN:

149572

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:

0.000864

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000281

AC:

AN:

135018

Hom.:

AF XY:

0.000393

AC XY:

AN XY:

73864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000419

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00161

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000104

AC:

139

AN:

1341256

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

106

AN XY:

662840

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000290

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00159

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000865

Gnomad4 OTH exome

AF:

0.0000544

GnomAD4 genome

AF:

0.0000334

AC:

AN:

149682

Hom.:

Cov.:

AF XY:

0.0000411

AC XY:

AN XY:

73056

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000863

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000480

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.000154

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 31, 2022

The c.155A>G (p.Y52C) alteration is located in exon 1 (coding exon 1) of the SLC35D2 gene. This alteration results from a A to G substitution at nucleotide position 155, causing the tyrosine (Y) at amino acid position 52 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Uncertain

-0.026

MutationAssessor

Uncertain

2.8

M;M;.

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-7.3

D;D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;B;D

Vest4

0.66

MutPred

0.52

Loss of glycosylation at T50 (P = 0.0995);Loss of glycosylation at T50 (P = 0.0995);Loss of glycosylation at T50 (P = 0.0995);

MVP

0.45

MPC

0.72

ClinPred

0.34

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.81

gMVP

0.52

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

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