13-99544698-G-A

Variant names:

• chr13-99544698-G-A
• rs9513627
• NM_004800.3:c.1150+703G>A

Variant summary

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

The NM_004800.3(TM9SF2):​c.1150+703G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,106 control chromosomes in the GnomAD database, including 55,781 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 0.85 (55781 hom., cov: 31)
• Consequence: TM9SF2 NM_004800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 8 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]

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 = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM9SF2	NM_004800.3	c.1150+703G>A		intron_variant	Intron 10 of 16	ENST00000376387.5	NP_004791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM9SF2	ENST00000376387.5	c.1150+703G>A		intron_variant	Intron 10 of 16	1	NM_004800.3	ENSP00000365567.3
TM9SF2	ENST00000642475.1	c.1150+703G>A		intron_variant	Intron 12 of 18			ENSP00000493515.1

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129572 AN: 151988 Hom.: 55749 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.937

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.852 AC: 129651 AN: 152106 Hom.: 55781 Cov.: 31 AF XY: 0.855 AC XY: 63555 AN XY: 74342

African (AFR) AF: 0.721 AC: 29883 AN: 41430

American (AMR) AF: 0.912 AC: 13938 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2924 AN: 3468

East Asian (EAS) AF: 0.903 AC: 4670 AN: 5170

South Asian (SAS) AF: 0.835 AC: 4025 AN: 4822

European-Finnish (FIN) AF: 0.916 AC: 9709 AN: 10598

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61546 AN: 68012

Other (OTH) AF: 0.868 AC: 1834 AN: 2112

Alfa AF: 0.885 Hom.: 165296

Bravo AF: 0.849

Asia WGS AF: 0.870 AC: 3027 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	0.35
DANN	Benign	0.40
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9513627; hg19: chr13-100196952;