Genetic Variant SLC35G2:p.Val151Leu (chr3-136854911-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025246.3(SLC35G2):c.451G>T(p.Val151Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

SLC35G2
NM_025246.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.45

Variant links:

Genes affected

SLC35G2 (HGNC:28480): (solute carrier family 35 member G2) Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC35G2 links:

NCK1-DT (HGNC:49645): (NCK1 divergent transcript)

NCK1-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35G2	NM_025246.3 link	c.451G>T	p.Val151Leu	missense_variant	Exon 2 of 2	ENST00000446465.3	NP_079522.2	Q8TBE7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35G2	ENST00000446465.3 link	c.451G>T	p.Val151Leu	missense_variant	Exon 2 of 2	1	NM_025246.3	ENSP00000400839.2		Q8TBE7

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251350

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135844

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727226

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.451G>T (p.V151L) alteration is located in exon 2 (coding exon 1) of the SLC35G2 gene. This alteration results from a G to T substitution at nucleotide position 451, causing the valine (V) at amino acid position 151 to be replaced by a leucine (L). 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

0.74

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.021

T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Benign

-0.83

MutationAssessor

Benign

-0.14

N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.32

N;N

REVEL

Benign

0.28

Sift

Benign

0.99

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.94

P;P

Vest4

0.88

MutPred

0.36

Gain of helix (P = 0.132);Gain of helix (P = 0.132);

MVP

0.58

MPC

0.53

ClinPred

0.37

GERP RS

5.6

Varity_R

0.10

gMVP

0.86

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