chr13-99465539-C-T

Variant names:

• chr13-99465539-C-T
• rs7325697
• ENST00000642146.1:c.-777+6857C>T

Variant summary

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

The ENST00000642146.1(TM9SF2):​c.-777+6857C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,148 control chromosomes in the GnomAD database, including 2,483 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 0.17 (2483 hom., cov: 32)
• Consequence: TM9SF2 ENST00000642146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 9 publications found

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]

ENSG00000297158 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.263 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.-777+6857C>T		intron_variant	Intron 3 of 4			ENSP00000494275.1
ENSG00000297158	ENST00000745902.1	n.102+4414C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26332 AN: 152030 Hom.: 2478 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.173 AC: 26356 AN: 152148 Hom.: 2483 Cov.: 32 AF XY: 0.174 AC XY: 12938 AN XY: 74388

African (AFR) AF: 0.237 AC: 9845 AN: 41486

American (AMR) AF: 0.119 AC: 1826 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3472

East Asian (EAS) AF: 0.0965 AC: 500 AN: 5180

South Asian (SAS) AF: 0.276 AC: 1328 AN: 4816

European-Finnish (FIN) AF: 0.121 AC: 1283 AN: 10604

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.152 AC: 10309 AN: 67984

Other (OTH) AF: 0.163 AC: 344 AN: 2110

Alfa AF: 0.145 Hom.: 1993

Bravo AF: 0.171

Asia WGS AF: 0.172 AC: 597 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	1.1
DANN	Benign	0.55
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs7325697; hg19: chr13-100117793;