1-159858105-T-C

Position:

• chr1-159858105-T-C

Variant summary

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

The NM_001013661.1(VSIG8):​c.415A>G​(p.Ile139Val) 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. 15/21 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)
• Consequence: VSIG8 NM_001013661.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

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:):

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=0.12093842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG8	NM_001013661.1	c.415A>G	p.Ile139Val	missense_variant	3/7	ENST00000368100.1	NP_001013683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSIG8	ENST00000368100.1	c.415A>G	p.Ile139Val	missense_variant	3/7	1	NM_001013661.1	ENSP00000357080.1
ENSG00000256029	ENST00000536779.5	n.*72A>G		non_coding_transcript_exon_variant	2/3	2		ENSP00000456698.1
ENSG00000256029	ENST00000536779.5	n.*72A>G		3_prime_UTR_variant	2/3	2		ENSP00000456698.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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

Aug 04, 2024

The c.415A>G (p.I139V) alteration is located in exon 3 (coding exon 3) of the VSIG8 gene. This alteration results from a A to G substitution at nucleotide position 415, causing the isoleucine (I) at amino acid position 139 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	0.079
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.80
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.027
Sift	Benign	1.0	T
Sift4G	Benign	0.13	T
Vest4		0.29
MutPred		0.44		Loss of sheet (P = 0.0817);
MVP		0.19
MPC		0.33
ClinPred		0.044	T
GERP RS		0.32
Varity_R		0.025
gMVP		0.13

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: chr1-159827895;