Variant 9-96383590-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007001.3(SLC35D2):c.45G>T(p.Glu15Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000031 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC35D2
NM_007001.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.803

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055649966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35D2	NM_007001.3 linkuse as main transcript	c.45G>T	p.Glu15Asp	missense_variant	1/12	ENST00000253270.13	NP_008932.2	Q76EJ3-1A0A024R9N5
SLC35D2	NM_001286990.2 linkuse as main transcript	c.45G>T	p.Glu15Asp	missense_variant	1/9		NP_001273919.1	Q76EJ3-2
SLC35D2	NR_104627.2 linkuse as main transcript	n.122G>T		non_coding_transcript_exon_variant	1/13
SLC35D2-HSD17B3	NR_182427.1 linkuse as main transcript	n.122G>T		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.45G>T	p.Glu15Asp	missense_variant	1/12	1	NM_007001.3	ENSP00000253270.7	Q76EJ3-1
SLC35D2	ENST00000375259.9 linkuse as main transcript	c.45G>T	p.Glu15Asp	missense_variant	1/9	1		ENSP00000364408.4	Q76EJ3-2
SLC35D2	ENST00000375257.2 linkuse as main transcript	c.45G>T	p.Glu15Asp	missense_variant	1/6	2		ENSP00000364406.1	Q5VZJ2
SLC35D2	ENST00000482643.2 linkuse as main transcript	n.91G>T		non_coding_transcript_exon_variant	1/9	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000311

AC:

AN:

1287976

Hom.:

Cov.:

AF XY:

0.00000472

AC XY:

AN XY:

635270

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:

0.0000144

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000292

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.0

DANN

Benign

0.94

DEOGEN2

Benign

0.012

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.36

T;T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.15

N;N;N

REVEL

Benign

0.025

Sift

Benign

0.62

T;T;T

Sift4G

Benign

0.53

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.028

MutPred

0.17

Gain of catalytic residue at G17 (P = 0.1096);Gain of catalytic residue at G17 (P = 0.1096);Gain of catalytic residue at G17 (P = 0.1096);

MVP

0.15

MPC

0.17

ClinPred

0.057

GERP RS

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.046

gMVP

0.12

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over