Variant 1-159854956-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001013661.1(VSIG8):c.1042C>T(p.Pro348Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000915 in 1,540,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

VSIG8
NM_001013661.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

Variant links:

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]

VSIG8 links:

(HGNC:):

links:

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

SNHG28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.19493744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
VSIG8	NM_001013661.1 linkuse as main transcript	c.1042C>T	p.Pro348Ser	missense_variant	7/7	ENST00000368100.1
SNHG28	NR_147123.1 linkuse as main transcript	n.82C>T		non_coding_transcript_exon_variant	1/4
LOC107985216	XR_001738261.2 linkuse as main transcript	n.110G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
VSIG8	ENST00000368100.1 linkuse as main transcript	c.1042C>T	p.Pro348Ser	missense_variant	7/7	1	NM_001013661.1	P1
	ENST00000608430.2 linkuse as main transcript	n.87G>A		non_coding_transcript_exon_variant	1/4
SNHG28	ENST00000676072.1 linkuse as main transcript	n.116C>T		non_coding_transcript_exon_variant	1/6

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000987

AC:

137

AN:

1388092

Hom.:

Cov.:

AF XY:

0.0000903

AC XY:

AN XY:

686554

show subpopulations

Gnomad4 AFR exome

AF:

0.0000669

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:

0.000123

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000274

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.1042C>T (p.P348S) alteration is located in exon 7 (coding exon 7) of the VSIG8 gene. This alteration results from a C to T substitution at nucleotide position 1042, causing the proline (P) at amino acid position 348 to be replaced by a serine (S). 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

0.15

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.60

M_CAP

Pathogenic

0.59

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

0.92

N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

2.0

REVEL

Benign

0.099

Sift

Benign

0.43

Sift4G

Uncertain

0.048

Vest4

0.068

MutPred

0.30

Gain of helix (P = 0.062);

MVP

0.36

MPC

0.40

ClinPred

0.99

GERP RS

5.0

Varity_R

0.12

gMVP

0.27

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over