12-118068522-TTCCTCCTCCTCC-TTCCTCCTCC

Variant names:

• chr12-118068522-TTCC-T
• rs67582641
• NM_019086.6:c.1419_1421delGGA

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_1421delGGA​(p.Glu474del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 1,570,240 control chromosomes in the GnomAD database, including 468 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (23 hom., cov: 19)
  • Exomes 𝑓: 0.027 (445 hom.)
• Consequence: VSIG10 NM_019086.6 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• 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 nfe. GnomAd4 allele frequency = 0.0193 (2904/150750) while in subpopulation NFE AF = 0.029 (1963/67680). AF 95% confidence interval is 0.0279. There are 23 homozygotes in GnomAd4. There are 1400 alleles in the male GnomAd4 subpopulation. Median coverage is 19. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 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_1421delGGA	p.Glu474del	disruptive_inframe_deletion	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_1421delGGA	p.Glu474del	disruptive_inframe_deletion	Exon 8 of 9	ENSP00000352172.5	Q8N0Z9-1
	VSIG10	ENST00000965107.1		c.1416_1418delGGA	p.Glu473del	disruptive_inframe_deletion	Exon 8 of 9	ENSP00000635166.1
	VSIG10	ENST00000965105.1		c.1158_1160delGGA	p.Glu387del	disruptive_inframe_deletion	Exon 7 of 8	ENSP00000635164.1

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2903 AN: 150638 Hom.: 23 Cov.: 19

Gnomad AFR AF: 0.00672

Gnomad AMI AF: 0.00442

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00295

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.0192

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0290

Gnomad OTH AF: 0.0208

GnomAD2 exomes AF: 0.0230 AC: 4980 AN: 216714 AF XY: 0.0235

Gnomad AFR exome AF: 0.00657

Gnomad AMR exome AF: 0.0177

Gnomad ASJ exome AF: 0.0228

Gnomad EAS exome AF: 0.00604

Gnomad FIN exome AF: 0.0218

Gnomad NFE exome AF: 0.0307

Gnomad OTH exome AF: 0.0245

GnomAD4 exome AF: 0.0270 AC: 38287 AN: 1419490 Hom.: 445 AF XY: 0.0267 AC XY: 18817 AN XY: 705072

African (AFR) AF: 0.00819 AC: 267 AN: 32608

American (AMR) AF: 0.0169 AC: 705 AN: 41686

Ashkenazi Jewish (ASJ) AF: 0.0188 AC: 472 AN: 25084

East Asian (EAS) AF: 0.00804 AC: 309 AN: 38424

South Asian (SAS) AF: 0.0168 AC: 1381 AN: 82006

European-Finnish (FIN) AF: 0.0219 AC: 1125 AN: 51466

Middle Eastern (MID) AF: 0.0436 AC: 246 AN: 5638

European-Non Finnish (NFE) AF: 0.0299 AC: 32388 AN: 1084120

Other (OTH) AF: 0.0238 AC: 1394 AN: 58458

GnomAD4 genome AF: 0.0193 AC: 2904 AN: 150750 Hom.: 23 Cov.: 19 AF XY: 0.0190 AC XY: 1400 AN XY: 73554

African (AFR) AF: 0.00675 AC: 277 AN: 41028

American (AMR) AF: 0.0182 AC: 274 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3464

East Asian (EAS) AF: 0.00296 AC: 15 AN: 5068

South Asian (SAS) AF: 0.0134 AC: 64 AN: 4760

European-Finnish (FIN) AF: 0.0192 AC: 199 AN: 10372

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0290 AC: 1963 AN: 67680

Other (OTH) AF: 0.0206 AC: 43 AN: 2086

Alfa AF: 0.0244 Hom.: 263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs67582641; hg19: chr12-118506327; COSMIC: COSV63652763; COSMIC: COSV63652763;