10-96528309-C-T

Variant names:

• chr10-96528309-C-T
• rs713251
• NM_020123.4:c.1395-132G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020123.4(TM9SF3):​c.1395-132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 768,396 control chromosomes in the GnomAD database, including 13,679 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3867 hom., cov: 32)
  • Exomes 𝑓: 0.17 (9812 hom.)
• Consequence: TM9SF3 NM_020123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM9SF3	NM_020123.4	c.1395-132G>A		intron_variant	Intron 11 of 14	ENST00000371142.9	NP_064508.3
TM9SF3	XM_011539976.3	c.1449-132G>A		intron_variant	Intron 11 of 14		XP_011538278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM9SF3	ENST00000371142.9	c.1395-132G>A		intron_variant	Intron 11 of 14	1	NM_020123.4	ENSP00000360184.4
TM9SF3	ENST00000649367.1	n.1733-132G>A		intron_variant	Intron 11 of 14
TM9SF3	ENST00000485093.1	n.-136G>A		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32259 AN: 151868 Hom.: 3864 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.169 AC: 104475 AN: 616408 Hom.: 9812 AF XY: 0.168 AC XY: 53125 AN XY: 315778

African (AFR) AF: 0.296 AC: 4200 AN: 14176

American (AMR) AF: 0.345 AC: 5760 AN: 16680

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 2649 AN: 13588

East Asian (EAS) AF: 0.143 AC: 4253 AN: 29738

South Asian (SAS) AF: 0.157 AC: 5792 AN: 36974

European-Finnish (FIN) AF: 0.113 AC: 3372 AN: 29970

Middle Eastern (MID) AF: 0.259 AC: 692 AN: 2668

European-Non Finnish (NFE) AF: 0.163 AC: 72186 AN: 442480

Other (OTH) AF: 0.185 AC: 5571 AN: 30134

GnomAD4 genome AF: 0.212 AC: 32287 AN: 151988 Hom.: 3867 Cov.: 32 AF XY: 0.210 AC XY: 15566 AN XY: 74296

African (AFR) AF: 0.295 AC: 12205 AN: 41438

American (AMR) AF: 0.305 AC: 4650 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3466

East Asian (EAS) AF: 0.159 AC: 825 AN: 5184

South Asian (SAS) AF: 0.155 AC: 750 AN: 4824

European-Finnish (FIN) AF: 0.115 AC: 1214 AN: 10582

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11425 AN: 67944

Other (OTH) AF: 0.218 AC: 458 AN: 2104

Alfa AF: 0.195 Hom.: 528

Bravo AF: 0.233

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs713251; hg19: chr10-98288066;