12-118068522-TTCCTCCTCCTCC-TTCCTCCTCCTCCTCC

Variant names:

• chr12-118068522-T-TTCC
• rs67582641
• NM_019086.6:c.1419_1421dupGGA

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 3 publications found

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]

LOC124903030 (HGNC:):

ACMG classification

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

• BP3: Nonframeshift variant in repetitive region in NM_019086.6
• 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019086.6. 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
	VSIG10	NM_019086.6	MANE Select	c.1419_1421dupGGA	p.Glu474dup	disruptive_inframe_insertion	Exon 8 of 9	NP_061959.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSIG10	ENST00000359236.10	TSL:1 MANE Select	c.1419_1421dupGGA	p.Glu474dup	disruptive_inframe_insertion	Exon 8 of 9	ENSP00000352172.5	Q8N0Z9-1
	VSIG10	ENST00000965107.1		c.1416_1418dupGGA	p.Glu473dup	disruptive_inframe_insertion	Exon 8 of 9	ENSP00000635166.1
	VSIG10	ENST00000965105.1		c.1158_1160dupGGA	p.Glu387dup	disruptive_inframe_insertion	Exon 7 of 8	ENSP00000635164.1

Frequencies

GnomAD3 genomes AF: 0.00609 AC: 917 AN: 150674 Hom.: 16 Cov.: 19

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

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.: 7 Cov.: 29 AF XY: 0.000888 AC XY: 641 AN XY: 721564

African (AFR) AF: 0.0222 AC: 737 AN: 33174

American (AMR) AF: 0.00133 AC: 57 AN: 42974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25942

East Asian (EAS) AF: 0.000436 AC: 17 AN: 38980

South Asian (SAS) AF: 0.000574 AC: 49 AN: 85298

European-Finnish (FIN) AF: 0.0000377 AC: 2 AN: 53060

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5754

European-Non Finnish (NFE) AF: 0.000455 AC: 504 AN: 1106480

Other (OTH) AF: 0.00140 AC: 84 AN: 60020

GnomAD4 genome AF: 0.00608 AC: 917 AN: 150786 Hom.: 16 Cov.: 19 AF XY: 0.00579 AC XY: 426 AN XY: 73568

African (AFR) AF: 0.0204 AC: 837 AN: 41024

American (AMR) AF: 0.00205 AC: 31 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000395 AC: 2 AN: 5068

South Asian (SAS) AF: 0.000420 AC: 2 AN: 4760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000502 AC: 34 AN: 67696

Other (OTH) AF: 0.00527 AC: 11 AN: 2086

Alfa AF: 0.000585 Hom.: 263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36
Mutation Taster		=90/10	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs67582641; hg19: chr12-118506327; COSMIC: COSV63652208; COSMIC: COSV63652208;