Genetic Variant NM_019086.6:c.1419_1421dupGGA (chr12-118068522-T-TTCC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_019086.6(VSIG10):c.1419_1421dupGGA(p.Glu474dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,602,468 control chromosomes in the GnomAD database, including 23 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0061 ( 16 hom., cov: 19)

Exomes 𝑓: 0.0010 ( 7 hom. )

Consequence

VSIG10
NM_019086.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.356

Publications

3 publications found

Variant links:

Genes affected

VSIG10 (HGNC:26078): (V-set and immunoglobulin domain containing 10) Predicted to enable cell adhesion molecule binding activity. Predicted to be involved in cell-cell adhesion. Predicted to be active in cell-cell junction. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

VSIG10 links:

LOC124903030 (HGNC:):

LOC124903030 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00608 (917/150786) while in subpopulation AFR AF = 0.0204 (837/41024). AF 95% confidence interval is 0.0193. There are 16 homozygotes in GnomAd4. There are 426 alleles in the male GnomAd4 subpopulation. Median coverage is 19. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSIG10	NM_019086.6 link	c.1419_1421dupGGA	p.Glu474dup	disruptive_inframe_insertion	Exon 8 of 9	ENST00000359236.10	NP_061959.2	Q8N0Z9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSIG10	ENST00000359236.10 link	c.1419_1421dupGGA	p.Glu474dup	disruptive_inframe_insertion	Exon 8 of 9	1	NM_019086.6	ENSP00000352172.5		Q8N0Z9-1

Frequencies

GnomAD3 genomes

AF:

0.00609

AC:

917

AN:

150674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00206

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000394

Gnomad SAS

AF:

0.000419

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000502

Gnomad OTH

AF:

0.00533

GnomAD2 exomes

AF:

0.00178

AC:

386

AN:

216714

AF XY:

0.00146

show subpopulations

Gnomad AFR exome

AF:

0.0201

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000460

Gnomad FIN exome

AF:

0.0000508

Gnomad NFE exome

AF:

0.000521

Gnomad OTH exome

AF:

0.000944

GnomAD4 exome

AF:

0.00100

AC:

1458

AN:

1451682

Hom.:

Cov.:

AF XY:

0.000888

AC XY:

641

AN XY:

721564

show subpopulations

African (AFR)

AF:

0.0222

AC:

737

AN:

33174

American (AMR)

AF:

0.00133

AC:

AN:

42974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25942

East Asian (EAS)

AF:

0.000436

AC:

AN:

38980

South Asian (SAS)

AF:

0.000574

AC:

AN:

85298

European-Finnish (FIN)

AF:

0.0000377

AC:

AN:

53060

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000455

AC:

504

AN:

1106480

Other (OTH)

AF:

0.00140

AC:

AN:

60020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

152

228

304

380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00608

AC:

917

AN:

150786

Hom.:

Cov.:

AF XY:

0.00579

AC XY:

426

AN XY:

73568

show subpopulations

African (AFR)

AF:

0.0204

AC:

837

AN:

41024

American (AMR)

AF:

0.00205

AC:

AN:

15100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000395

AC:

AN:

5068

South Asian (SAS)

AF:

0.000420

AC:

AN:

4760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000502

AC:

AN:

67696

Other (OTH)

AF:

0.00527

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

129

172

215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.000585

Hom.:

263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.36

Mutation Taster

=90/10

polymorphism

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over