19-51341161-C-A

Position:

• chr19-51341161-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001163922.3(VSIG10L):​c.887G>T​(p.Gly296Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VSIG10L NM_001163922.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.461

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-AS1 (HGNC:55282): (VSIG10L antisense RNA 1)

ACMG classification

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=0.09729266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG10L	NM_001163922.3	c.887G>T	p.Gly296Val	missense_variant	2/10	ENST00000335624.5	NP_001157394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSIG10L	ENST00000335624.5	c.887G>T	p.Gly296Val	missense_variant	2/10	5	NM_001163922.3	ENSP00000335623	P1
VSIG10L-AS1	ENST00000594311.1	n.119C>A		non_coding_transcript_exon_variant	2/4	5
VSIG10L-AS1	ENST00000601148.5	n.119C>A		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1367608 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 671792

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2022

The c.887G>T (p.G296V) alteration is located in exon 2 (coding exon 2) of the VSIG10L gene. This alteration results from a G to T substitution at nucleotide position 887, causing the glycine (G) at amino acid position 296 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	0.20
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	M
MutationTaster	Benign	0.97	N
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.014
Sift	Benign	0.43	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.35		Loss of catalytic residue at V297 (P = 0.097);
MVP		0.16
ClinPred		0.065	T
GERP RS		0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.12
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-51844415; COSMIC: COSV100164572; COSMIC: COSV100164572;