rs6667912

Variant names:

• chr1-201148730-C-G
• rs6667912
• NM_001288565.2:c.159-1882G>C

Variant summary

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

The NM_001288565.2(TMEM9):​c.159-1882G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,102 control chromosomes in the GnomAD database, including 9,186 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 0.34 (9186 hom., cov: 33)
• Consequence: TMEM9 NM_001288565.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 5 publications found

Genes affected

TMEM9 (HGNC:18823): (transmembrane protein 9) Involved in intracellular pH reduction; positive regulation of canonical Wnt signaling pathway; and proton-transporting V-type ATPase complex assembly. Located in bounding membrane of organelle; intercellular bridge; and mitotic spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM9	NM_001288565.2	c.159-1882G>C		intron_variant	Intron 2 of 4	ENST00000367330.6	NP_001275494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM9	ENST00000367330.6	c.159-1882G>C		intron_variant	Intron 2 of 4	1	NM_001288565.2	ENSP00000356299.1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52004 AN: 151984 Hom.: 9176 Cov.: 33

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.342 AC: 52038 AN: 152102 Hom.: 9186 Cov.: 33 AF XY: 0.339 AC XY: 25220 AN XY: 74370

African (AFR) AF: 0.398 AC: 16509 AN: 41484

American (AMR) AF: 0.301 AC: 4607 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 941 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2034 AN: 5160

South Asian (SAS) AF: 0.306 AC: 1475 AN: 4816

European-Finnish (FIN) AF: 0.303 AC: 3205 AN: 10582

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22252 AN: 67984

Other (OTH) AF: 0.332 AC: 701 AN: 2110

Alfa AF: 0.340 Hom.: 1084

Bravo AF: 0.344

Asia WGS AF: 0.351 AC: 1220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.56
PhyloP100		-0.24
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: rs6667912; hg19: chr1-201117858;