rs11616269

Positions:

• chr13-99454633-T-C

Variant summary

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

The ENST00000642146.1(TM9SF2):​c.-925+2408T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,042 control chromosomes in the GnomAD database, including 1,401 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 0.13 (1401 hom., cov: 31)
• Consequence: TM9SF2 ENST00000642146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

Genes affected

TM9SF2 (HGNC:11865): (transmembrane 9 superfamily member 2) This gene encodes a member of the transmembrane 9 superfamily. The encoded 76 kDa protein localizes to early endosomes in human cells. The encoded protein possesses a conserved and highly hydrophobic C-terminal domain which contains nine transmembrane domains. The protein may play a role in small molecule transport or act as an ion channel. A pseudogene associated with this gene is located on the X chromosome. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TM9SF2	ENST00000642146.1	c.-925+2408T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20105 AN: 151942 Hom.: 1396 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.0756

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.138

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.132 AC: 20134 AN: 152042 Hom.: 1401 Cov.: 31 AF XY: 0.131 AC XY: 9747 AN XY: 74324

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.0758

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.137

Alfa AF: 0.138 Hom.: 2049

Bravo AF: 0.132

Asia WGS AF: 0.102 AC: 355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.77
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11616269; hg19: chr13-100106887;