10-96559738-TA-T

Variant names:

• chr10-96559738-TA-T
• rs745424345
• NM_020123.4:c.583-3delT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_020123.4(TM9SF3):​c.583-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 1,542,036 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: TM9SF3 NM_020123.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.133
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 10-96559738-TA-T is Benign according to our data. Variant chr10-96559738-TA-T is described in ClinVar as [Benign]. Clinvar id is 2991543.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM9SF3	NM_020123.4	c.583-3delT		splice_region_variant, intron_variant	Intron 4 of 14	ENST00000371142.9	NP_064508.3
TM9SF3	XM_011539976.3	c.637-3delT		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.583-3delT		splice_region_variant, intron_variant	Intron 4 of 14	1	NM_020123.4	ENSP00000360184.4
TM9SF3	ENST00000443638.1	c.451-3delT		splice_region_variant, intron_variant	Intron 4 of 6	3		ENSP00000401152.1
TM9SF3	ENST00000464654.1	n.545-3delT		splice_region_variant, intron_variant	Intron 4 of 5	5
TM9SF3	ENST00000649367.1	n.921-3delT		splice_region_variant, intron_variant	Intron 4 of 14

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000117 AC: 20 AN: 170936 AF XY: 0.000110

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000207

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.000154

Gnomad FIN exome AF: 0.0000665

Gnomad NFE exome AF: 0.000138

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000496 AC: 69 AN: 1389794 Hom.: 0 Cov.: 24 AF XY: 0.0000525 AC XY: 36 AN XY: 685736

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

African (AFR) AF: 0.00 AC: 0 AN: 31822

American (AMR) AF: 0.000131 AC: 5 AN: 38264

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

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

South Asian (SAS) AF: 0.0000517 AC: 4 AN: 77368

European-Finnish (FIN) AF: 0.0000827 AC: 4 AN: 48364

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

European-Non Finnish (NFE) AF: 0.0000515 AC: 55 AN: 1068084

Other (OTH) AF: 0.0000174 AC: 1 AN: 57508

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74394

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 01, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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; COSMIC: COSV100951901; COSMIC: COSV100951901;