1-159854827-C-T

Position:

• chr1-159854827-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013661.1(VSIG8):​c.1171G>A​(p.Val391Ile) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VSIG8 NM_001013661.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

Genes affected

VSIG8 (HGNC:32063): (V-set and immunoglobulin domain containing 8) Enables RNA binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000256029 (HGNC:):

SNHG28 (HGNC:27647): (small nucleolar RNA host gene 28) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05414155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG8	NM_001013661.1	c.1171G>A	p.Val391Ile	missense_variant	7/7	ENST00000368100.1	NP_001013683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSIG8	ENST00000368100.1	c.1171G>A	p.Val391Ile	missense_variant	7/7	1	NM_001013661.1	ENSP00000357080.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1345848 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 664048

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.: 33

Bravo AF: 0.00000756

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

Jun 26, 2024

The c.1171G>A (p.V391I) alteration is located in exon 7 (coding exon 7) of the VSIG8 gene. This alteration results from a G to A substitution at nucleotide position 1171, causing the valine (V) at amino acid position 391 to be replaced by an isoleucine (I). 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	0.078
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.022
Sift	Benign	0.81	T
Sift4G	Benign	0.38	T
Vest4		0.088
MutPred		0.15		Loss of ubiquitination at K392 (P = 0.069);
MVP		0.040
MPC		0.32
ClinPred		0.67	D
GERP RS		3.3
Varity_R		0.026
gMVP		0.14

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

Other links and lift over

dbSNP: rs936816781; hg19: chr1-159824617;