3-136855131-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025246.3(SLC35G2):​c.671C>T​(p.Ala224Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SLC35G2
NM_025246.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.67
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]
NCK1-DT (HGNC:49645): (NCK1 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08064479).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC35G2NM_025246.3 linkc.671C>T p.Ala224Val 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
SLC35G2ENST00000446465.3 linkc.671C>T p.Ala224Val missense_variant Exon 2 of 2 1 NM_025246.3 ENSP00000400839.2 Q8TBE7

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152192
Hom.:
0
Cov.:
32
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
39
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152192
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74358
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:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 17, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.671C>T (p.A224V) alteration is located in exon 2 (coding exon 1) of the SLC35G2 gene. This alteration results from a C to T substitution at nucleotide position 671, causing the alanine (A) at amino acid position 224 to be replaced by a valine (V). 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
0.064
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
16
DANN
Benign
0.85
DEOGEN2
Benign
0.013
T;T
Eigen
Benign
-0.20
Eigen_PC
Benign
0.074
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.82
.;T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.081
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.55
N;N
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
1.4
N;N
REVEL
Benign
0.039
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.078
MutPred
0.39
Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);
MVP
0.46
MPC
0.12
ClinPred
0.32
T
GERP RS
5.7
Varity_R
0.043
gMVP
0.48

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.

Other links and lift over

dbSNP: rs1275409451; hg19: chr3-136573973; API