Genetic Variant VSIG1:p.Thr354Lys (chrX-108077278-C-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_182607.5(VSIG1):c.1061C>A(p.Thr354Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000967 in 1,210,321 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., 15 hem., cov: 23)

Exomes 𝑓: 0.000046 ( 0 hom. 12 hem. )

Consequence

VSIG1
NM_182607.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -2.21

Publications

0 publications found

Variant links:

Genes affected

VSIG1 (HGNC:28675): (V-set and immunoglobulin domain containing 1) This gene encodes a member of the junctional adhesion molecule (JAM) family. The encoded protein contains multiple glycosylation sites at the N-terminal region, and multiple phosphorylation sites and glutamic acid/proline (EP) repeats at the C-terminal region. The gene is expressed in normal stomach and testis, as well as in gastric, esophageal and ovarian cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

VSIG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055253804).

BP6

Variant X-108077278-C-A is Benign according to our data. Variant chrX-108077278-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 738138.

BS2

High Hemizygotes in GnomAd4 at 15 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182607.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSIG1	NM_182607.5	MANE Select	c.1061C>A	p.Thr354Lys	missense	Exon 7 of 7	NP_872413.1	Q86XK7-1
	VSIG1	NM_001170553.2		c.1169C>A	p.Thr390Lys	missense	Exon 8 of 8	NP_001164024.1	Q86XK7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSIG1	ENST00000217957.10	TSL:1 MANE Select	c.1061C>A	p.Thr354Lys	missense	Exon 7 of 7	ENSP00000217957.3	Q86XK7-1
	VSIG1	ENST00000415430.7	TSL:2	c.1169C>A	p.Thr390Lys	missense	Exon 8 of 8	ENSP00000402219.3	Q86XK7-2

Frequencies

GnomAD3 genomes

AF:

0.000580

AC:

AN:

112020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000946

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:

0.000668

GnomAD2 exomes

AF:

0.000153

AC:

AN:

183309

AF XY:

0.0000885

show subpopulations

Gnomad AFR exome

AF:

0.00198

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000464

AC:

AN:

1098250

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

363610

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

26402

American (AMR)

AF:

0.0000852

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40531

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

842139

Other (OTH)

AF:

0.000130

AC:

AN:

46095

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000589

AC:

AN:

112071

Hom.:

Cov.:

AF XY:

0.000438

AC XY:

AN XY:

34235

show subpopulations

African (AFR)

AF:

0.00208

AC:

AN:

30835

American (AMR)

AF:

0.0000945

AC:

AN:

10582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3563

South Asian (SAS)

AF:

0.00

AC:

AN:

2694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6099

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53225

Other (OTH)

AF:

0.000659

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000127

Hom.:

Bravo

AF:

0.000597

ESP6500AA

AF:

0.00261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000222

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.022

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.019

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-2.2

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.66

REVEL

Benign

0.0080

Sift

Benign

0.18

Sift4G

Uncertain

0.048

Polyphen

0.029

Vest4

0.20

MVP

0.030

MPC

0.22

ClinPred

0.013

GERP RS

-6.9

Varity_R

0.052

gMVP

0.13

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over