Genetic Variant SLC35G2:p.Glu50Lys (chr3-136854608-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_025246.3(SLC35G2):c.148G>A(p.Glu50Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,612,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

SLC35G2
NM_025246.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.29

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3456331).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35G2	NM_025246.3 link	c.148G>A	p.Glu50Lys	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.148G>A	p.Glu50Lys	missense_variant	Exon 2 of 2	1	NM_025246.3	ENSP00000400839.2		Q8TBE7

Frequencies

GnomAD3 genomes

AF:

0.0000724

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000681

AC:

AN:

249700

Hom.:

AF XY:

0.0000667

AC XY:

AN XY:

135016

show subpopulations

Gnomad AFR exome

AF:

0.000125

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:

0.000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000174

AC:

254

AN:

1460558

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

113

AN XY:

726458

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000225

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:

0.000217

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000724

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.0000718

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000273

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

Sep 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.148G>A (p.E50K) alteration is located in exon 2 (coding exon 1) of the SLC35G2 gene. This alteration results from a G to A substitution at nucleotide position 148, causing the glutamic acid (E) at amino acid position 50 to be replaced by a lysine (K). 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

0.10

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

.;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

L;L

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.25

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.88

P;P

Vest4

0.61

MVP

0.51

MPC

0.42

ClinPred

0.21

GERP RS

5.5

Varity_R

0.41

gMVP

0.66

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