Variant chr1-159854907-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001013661.1(VSIG8):c.1091C>G(p.Pro364Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,488,376 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 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

VSIG8
NM_001013661.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33516955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
VSIG8	NM_001013661.1 linkuse as main transcript	c.1091C>G	p.Pro364Arg	missense_variant	7/7	ENST00000368100.1
LOC107985216	XR_001738261.2 linkuse as main transcript	n.61G>C		non_coding_transcript_exon_variant	1/2
SNHG28	NR_147123.1 linkuse as main transcript	n.116+15C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
VSIG8	ENST00000368100.1 linkuse as main transcript	c.1091C>G	p.Pro364Arg	missense_variant	7/7	1	NM_001013661.1	P1
	ENST00000608430.2 linkuse as main transcript	n.38G>C		non_coding_transcript_exon_variant	1/4
SNHG28	ENST00000676072.1 linkuse as main transcript	n.150+15C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000412

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000276

AC:

AN:

83426

Hom.:

AF XY:

0.000256

AC XY:

AN XY:

46918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000394

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000573

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.000394

GnomAD4 exome

AF:

0.000188

AC:

251

AN:

1336068

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

118

AN XY:

657796

show subpopulations

Gnomad4 AFR exome

AF:

0.000223

Gnomad4 AMR exome

AF:

0.000312

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000954

Gnomad4 SAS exome

AF:

0.000412

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000180

Gnomad4 OTH exome

AF:

0.000180

GnomAD4 genome

AF:

0.000243

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000461

Hom.:

Bravo

AF:

0.000321

ExAC

AF:

0.0000363

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

Nov 03, 2022

The c.1091C>G (p.P364R) alteration is located in exon 7 (coding exon 7) of the VSIG8 gene. This alteration results from a C to G substitution at nucleotide position 1091, causing the proline (P) at amino acid position 364 to be replaced by an arginine (R). 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

0.089

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.99

N;D

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.20

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.24

MVP

0.44

MPC

1.0

ClinPred

0.30

GERP RS

2.8

Varity_R

0.46

gMVP

0.31

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