Genetic Variant VSIG10L:p.Gly758Arg (chr19-51337271-C-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_001163922.3(VSIG10L):c.2272G>A(p.Gly758Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000593 in 1,550,638 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000036 ( 1 hom. )

Consequence

VSIG10L
NM_001163922.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

Variant links:

Genes affected

VSIG10L (HGNC:27111): (V-set and immunoglobulin domain containing 10 like) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

VSIG10L 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
VSIG10L	NM_001163922.3 link	c.2272G>A	p.Gly758Arg	missense_variant	Exon 7 of 10	ENST00000335624.5	NP_001157394.1	Q86VR7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSIG10L	ENST00000335624.5 link	c.2272G>A	p.Gly758Arg	missense_variant	Exon 7 of 10	5	NM_001163922.3	ENSP00000335623.3		Q86VR7-1
VSIG10L	ENST00000600663.1 link	n.890G>A		non_coding_transcript_exon_variant	Exon 4 of 7	1

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000390

AC:

AN:

154016

Hom.:

AF XY:

0.0000367

AC XY:

AN XY:

81758

show subpopulations

Gnomad AFR exome

AF:

0.000756

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000365

AC:

AN:

1398418

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

689554

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.0000280

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:

0.00

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.000269

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.000965

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000229

Hom.:

Bravo

AF:

0.000385

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2272G>A (p.G758R) alteration is located in exon 7 (coding exon 7) of the VSIG10L gene. This alteration results from a G to A substitution at nucleotide position 2272, causing the glycine (G) at amino acid position 758 to be replaced by an arginine (R). 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

0.87

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.44

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.2

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.22

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.49

MutPred

0.35

Gain of sheet (P = 0.039);

MVP

0.23

ClinPred

0.45

GERP RS

4.8

Varity_R

0.54

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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