19-51341781-C-A

Variant names:

• chr19-51341781-C-A
• rs1378092526
• NM_001163922.3:c.267G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001163922.3(VSIG10L):​c.267G>T​(p.Met89Ile) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VSIG10L NM_001163922.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040605634).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163922.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSIG10L	NM_001163922.3	MANE Select	c.267G>T	p.Met89Ile	missense	Exon 2 of 10	NP_001157394.1	Q86VR7-1
	VSIG10L-AS1	NR_186316.1		n.808-69C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSIG10L	ENST00000335624.5	TSL:5 MANE Select	c.267G>T	p.Met89Ile	missense	Exon 2 of 10	ENSP00000335623.3	Q86VR7-1
	VSIG10L	ENST00000915571.1		c.267G>T	p.Met89Ile	missense	Exon 2 of 11	ENSP00000585630.1
	VSIG10L-AS1	ENST00000594311.1	TSL:5	n.133-91C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 77

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000338 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.68
DANN	Benign	0.90
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.083
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.013
Sift	Benign	0.17	T
Sift4G	Benign	0.37	T
Polyphen		0.0070	B
Vest4		0.094
MutPred		0.24		Gain of catalytic residue at M89 (P = 0.0028)
MVP		0.048
ClinPred		0.025	T
GERP RS		0.45
PromoterAI		-0.059	Neutral
Varity_R		0.069
gMVP		0.048
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1378092526; hg19: chr19-51845035;