rs11616269

Variant names:

• chr13-99454633-T-C
• rs11616269
• ENST00000642146.1:c.-925+2408T>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM9SF2	ENST00000642146.1	c.-925+2408T>C		intron_variant	Intron 2 of 4			ENSP00000494275.1

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;