9-96383499-T-C

Position:

chr9-96383499-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_007001.3(SLC35D2):c.136A>G(p.Lys46Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000586 in 1,536,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

SLC35D2
NM_007001.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.761

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35D2	NM_007001.3 linkuse as main transcript	c.136A>G	p.Lys46Glu	missense_variant	1/12	ENST00000253270.13	NP_008932.2	Q76EJ3-1A0A024R9N5
SLC35D2	NM_001286990.2 linkuse as main transcript	c.136A>G	p.Lys46Glu	missense_variant	1/9		NP_001273919.1	Q76EJ3-2
SLC35D2	NR_104627.2 linkuse as main transcript	n.213A>G		non_coding_transcript_exon_variant	1/13
SLC35D2-HSD17B3	NR_182427.1 linkuse as main transcript	n.213A>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.136A>G	p.Lys46Glu	missense_variant	1/12	1	NM_007001.3	ENSP00000253270.7	Q76EJ3-1
SLC35D2	ENST00000375259.9 linkuse as main transcript	c.136A>G	p.Lys46Glu	missense_variant	1/9	1		ENSP00000364408.4	Q76EJ3-2
SLC35D2	ENST00000375257.2 linkuse as main transcript	c.136A>G	p.Lys46Glu	missense_variant	1/6	2		ENSP00000364406.1	Q5VZJ2
SLC35D2	ENST00000482643.2 linkuse as main transcript	n.182A>G		non_coding_transcript_exon_variant	1/9	5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151876

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000293

AC:

AN:

136470

Hom.:

AF XY:

0.0000537

AC XY:

AN XY:

74556

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000179

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000578

AC:

AN:

1385012

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

683816

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000888

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.32e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151876

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74180

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000287

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

Nov 30, 2022

The c.136A>G (p.K46E) 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 136, causing the lysine (K) at amino acid position 46 to be replaced by a glutamic acid (E). 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

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

D;.;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Pathogenic

0.97

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Uncertain

0.79

MutationAssessor

Pathogenic

3.3

M;M;.

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Pathogenic

0.86

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.73

MutPred

0.58

Loss of methylation at K46 (P = 0.0025);Loss of methylation at K46 (P = 0.0025);Loss of methylation at K46 (P = 0.0025);

MVP

0.71

MPC

0.28

ClinPred

0.69

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.97

gMVP

0.87

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