10-96559738-TAAAA-TA

Variant names:

• chr10-96559738-TAAA-T
• rs745424345
• NM_020123.4:c.583-5_583-3delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020123.4(TM9SF3):​c.583-5_583-3delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,389,972 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TM9SF3 NM_020123.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• 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.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM9SF3	NM_020123.4	c.583-5_583-3delTTT		splice_region_variant, intron_variant	Intron 4 of 14	ENST00000371142.9	NP_064508.3
TM9SF3	XM_011539976.3	c.637-5_637-3delTTT		splice_region_variant, intron_variant	Intron 4 of 14		XP_011538278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM9SF3	ENST00000371142.9	c.583-5_583-3delTTT		splice_region_variant, intron_variant	Intron 4 of 14	1	NM_020123.4	ENSP00000360184.4
TM9SF3	ENST00000443638.1	c.451-5_451-3delTTT		splice_region_variant, intron_variant	Intron 4 of 6	3		ENSP00000401152.1
TM9SF3	ENST00000464654.1	n.545-5_545-3delTTT		splice_region_variant, intron_variant	Intron 4 of 5	5
TM9SF3	ENST00000649367.1	n.921-5_921-3delTTT		splice_region_variant, intron_variant	Intron 4 of 14

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000585 AC: 1 AN: 170936 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000138

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1389972 Hom.: 0 AF XY: 0.00000146 AC XY: 1 AN XY: 685816

African (AFR) AF: 0.00 AC: 0 AN: 31828

American (AMR) AF: 0.00 AC: 0 AN: 38280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24864

East Asian (EAS) AF: 0.00 AC: 0 AN: 38160

South Asian (SAS) AF: 0.00 AC: 0 AN: 77392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5360

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1068194

Other (OTH) AF: 0.00 AC: 0 AN: 57516

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000434 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs745424345; hg19: chr10-98319495;