rs7525970

Variant names:

• chr1-201149874-C-G
• rs7525970
• NM_001288565.2:c.158+1887G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001288565.2(TMEM9):​c.158+1887G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 152,304 control chromosomes in the GnomAD database, including 38 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 0.012 (38 hom., cov: 32)
• Consequence: TMEM9 NM_001288565.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 1 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=-0.9).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0122 (1863/152304) while in subpopulation AFR AF = 0.0429 (1784/41556). AF 95% confidence interval is 0.0413. There are 38 homozygotes in GnomAd4. There are 879 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM9	NM_001288565.2	c.158+1887G>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.158+1887G>C		intron_variant	Intron 2 of 4	1	NM_001288565.2	ENSP00000356299.1

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1864 AN: 152186 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00813

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

GnomAD4 genome AF: 0.0122 AC: 1863 AN: 152304 Hom.: 38 Cov.: 32 AF XY: 0.0118 AC XY: 879 AN XY: 74486

African (AFR) AF: 0.0429 AC: 1784 AN: 41556

American (AMR) AF: 0.00340 AC: 52 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68028

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.0105 Hom.: 7

Bravo AF: 0.0139

Asia WGS AF: 0.00260 AC: 9 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	1.4
DANN	Benign	0.55
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism

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: rs7525970; hg19: chr1-201119002;