rs17391197

Positions:

• chr10-96522403-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020123.4(TM9SF3):​c.1703-73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,145,324 control chromosomes in the GnomAD database, including 12,043 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 0.11 (1111 hom., cov: 32)
  • Exomes 𝑓: 0.14 (10932 hom.)
• Consequence: TM9SF3 NM_020123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TM9SF3	NM_020123.4	c.1703-73T>C		intron_variant		ENST00000371142.9
TM9SF3	XM_011539976.3	c.1757-73T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TM9SF3	ENST00000371142.9	c.1703-73T>C		intron_variant		1	NM_020123.4	P1
TM9SF3	ENST00000485093.1	n.354-73T>C		intron_variant, non_coding_transcript_variant		5
TM9SF3	ENST00000649367.1	n.2041-73T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16828 AN: 151542 Hom.: 1108 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0147

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.143 AC: 141750 AN: 993664 Hom.: 10932 AF XY: 0.143 AC XY: 72062 AN XY: 504038

Gnomad4 AFR exome AF: 0.0628

Gnomad4 AMR exome AF: 0.0605

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.0115

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.111 AC: 16832 AN: 151660 Hom.: 1111 Cov.: 32 AF XY: 0.110 AC XY: 8135 AN XY: 74182

Gnomad4 AFR AF: 0.0641

Gnomad4 AMR AF: 0.0764

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.106

Alfa AF: 0.130 Hom.: 385

Bravo AF: 0.105

Asia WGS AF: 0.0690 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17391197; hg19: chr10-98282160; COSMIC: COSV64456946;