17-35193623-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_152462.2(SLC35G3):​c.685G>A​(p.Val229Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,612,040 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

SLC35G3
NM_152462.2 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.779
Variant links:
Genes affected
SLC35G3 (HGNC:26848): (solute carrier family 35 member G3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.069945455).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC35G3NM_152462.2 linkc.685G>A p.Val229Met missense_variant Exon 1 of 1 ENST00000297307.7 NP_689675.1 Q8N808

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC35G3ENST00000297307.7 linkc.685G>A p.Val229Met missense_variant Exon 1 of 1 6 NM_152462.2 ENSP00000297307.5 Q8N808

Frequencies

GnomAD3 genomes
AF:
0.000250
AC:
38
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000397
Gnomad OTH
AF:
0.000958
GnomAD3 exomes
AF:
0.000323
AC:
81
AN:
250838
Hom.:
1
AF XY:
0.000354
AC XY:
48
AN XY:
135662
show subpopulations
Gnomad AFR exome
AF:
0.0000621
Gnomad AMR exome
AF:
0.000260
Gnomad ASJ exome
AF:
0.000198
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000503
Gnomad OTH exome
AF:
0.000491
GnomAD4 exome
AF:
0.000321
AC:
468
AN:
1459714
Hom.:
2
Cov.:
32
AF XY:
0.000337
AC XY:
245
AN XY:
726164
show subpopulations
Gnomad4 AFR exome
AF:
0.000599
Gnomad4 AMR exome
AF:
0.000268
Gnomad4 ASJ exome
AF:
0.000459
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000360
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000296
Gnomad4 OTH exome
AF:
0.000648
GnomAD4 genome
AF:
0.000249
AC:
38
AN:
152326
Hom.:
0
Cov.:
32
AF XY:
0.000228
AC XY:
17
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000397
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.000371
Hom.:
0
Bravo
AF:
0.000280
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000288
AC:
35
EpiCase
AF:
0.000654
EpiControl
AF:
0.00107

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.685G>A (p.V229M) alteration is located in exon 1 (coding exon 1) of the SLC35G3 gene. This alteration results from a G to A substitution at nucleotide position 685, causing the valine (V) at amino acid position 229 to be replaced by a methionine (M). 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
0.21
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.015
T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.024
N
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.070
T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.68
N
REVEL
Benign
0.095
Sift
Uncertain
0.018
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.077
MVP
0.41
MPC
0.53
ClinPred
0.064
T
Varity_R
0.068
gMVP
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs149382529; hg19: chr17-33520642; API