10-96551294-C-CAGCAAATATCTGACATCCAGAACA

Variant names:

• chr10-96551294-C-CAGCAAATATCTGACATCCAGAACA
• rs2134143642
• NM_020123.4:c.909_910insTGTTCTGGATGTCAGATATTTGCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_020123.4(TM9SF3):​c.909_910insTGTTCTGGATGTCAGATATTTGCT​(p.Ala303_Val304insCysSerGlyCysGlnIlePheAla) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TM9SF3 NM_020123.4 conservative_inframe_insertion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.0220
• Publications: 0 publications found

Genes affected

TM9SF3 (HGNC:21529): (transmembrane 9 superfamily member 3) Predicted to be involved in protein localization to membrane. Predicted to be located in exocytic vesicle. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_020123.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM9SF3	NM_020123.4	c.909_910insTGTTCTGGATGTCAGATATTTGCT	p.Ala303_Val304insCysSerGlyCysGlnIlePheAla	conservative_inframe_insertion	Exon 7 of 15	ENST00000371142.9	NP_064508.3
TM9SF3	XM_011539976.3	c.963_964insTGTTCTGGATGTCAGATATTTGCT	p.Ala321_Val322insCysSerGlyCysGlnIlePheAla	conservative_inframe_insertion	Exon 7 of 15		XP_011538278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM9SF3	ENST00000371142.9	c.909_910insTGTTCTGGATGTCAGATATTTGCT	p.Ala303_Val304insCysSerGlyCysGlnIlePheAla	conservative_inframe_insertion	Exon 7 of 15	1	NM_020123.4	ENSP00000360184.4
TM9SF3	ENST00000490192.1	n.133_134insTGTTCTGGATGTCAGATATTTGCT		non_coding_transcript_exon_variant	Exon 2 of 4	4
TM9SF3	ENST00000649367.1	n.1247_1248insTGTTCTGGATGTCAGATATTTGCT		non_coding_transcript_exon_variant	Exon 7 of 15
TM9SF3	ENST00000443638.1	c.*16_*17insTGTTCTGGATGTCAGATATTTGCT		downstream_gene_variant		3		ENSP00000401152.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Jul 15, 2021

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

Gene of uncertain significance -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.022

Splicing

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

Other links and lift over

dbSNP: rs2134143642; hg19: chr10-98311051;