12-118068522-T-TTCCTCCTCCTCCTCC

Variant names:

• chr12-118068522-T-TTCCTCCTCCTCCTCC
• rs67582641
• NM_019086.6:c.1407_1421dupGGAGGAGGAGGAGGA

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_019086.6(VSIG10):​c.1407_1421dupGGAGGAGGAGGAGGA​(p.Glu470_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 0.000000689 in 1,451,718 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: VSIG10 NM_019086.6 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

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

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.1407_1421dupGGAGGAGGAGGAGGA	p.Glu470_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.1407_1421dupGGAGGAGGAGGAGGA	p.Glu470_Glu474dup	disruptive_inframe_insertion	Exon 8 of 9	ENSP00000352172.5	Q8N0Z9-1
	VSIG10	ENST00000965107.1		c.1404_1418dupGGAGGAGGAGGAGGA	p.Glu469_Glu473dup	disruptive_inframe_insertion	Exon 8 of 9	ENSP00000635166.1
	VSIG10	ENST00000965105.1		c.1146_1160dupGGAGGAGGAGGAGGA	p.Glu383_Glu387dup	disruptive_inframe_insertion	Exon 7 of 8	ENSP00000635164.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451718 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 721580

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000301 AC: 1 AN: 33178

American (AMR) AF: 0.00 AC: 0 AN: 42976

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 38980

South Asian (SAS) AF: 0.00 AC: 0 AN: 85300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106508

Other (OTH) AF: 0.00 AC: 0 AN: 60020

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36

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;