chr1-159856628-T-A

Position:

• chr1-159856628-T-A

Variant summary

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

The NM_001013661.1(VSIG8):​c.668A>T​(p.Asp223Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,108 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: VSIG8 NM_001013661.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36

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]

(HGNC:):

ACMG classification

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/exons	MANE	UniProt
VSIG8	NM_001013661.1	c.668A>T	p.Asp223Val	missense_variant	5/7	ENST00000368100.1
LOC107985216	XR_001738261.2	n.1257+525T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSIG8	ENST00000368100.1	c.668A>T	p.Asp223Val	missense_variant	5/7	1	NM_001013661.1	P1
	ENST00000608430.2	n.328+504T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74314

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

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

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 26, 2022

The c.668A>T (p.D223V) alteration is located in exon 5 (coding exon 5) of the VSIG8 gene. This alteration results from a A to T substitution at nucleotide position 668, causing the aspartic acid (D) at amino acid position 223 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	Uncertain	0.45
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	27
DANN	Benign	0.67
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.94	L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.29
Sift	Benign	0.30	T
Sift4G	Pathogenic	0.0	D
Vest4		0.65
MutPred		0.47		Loss of ubiquitination at K227 (P = 0.043);
MVP		0.37
MPC		1.4
ClinPred		0.88	D
GERP RS		5.1
Varity_R		0.22
gMVP		0.66

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

LitVar

Other links and lift over

dbSNP: rs1648837352; hg19: chr1-159826418;