1-201143853-A-G

Variant names:

• chr1-201143853-A-G
• rs8158
• NM_001288565.2:c.366T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001288565.2(TMEM9):​c.366T>C​(p.Tyr122Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,613,680 control chromosomes in the GnomAD database, including 462,034 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 0.73 (40465 hom., cov: 32)
  • Exomes 𝑓: 0.76 (421569 hom.)
• Consequence: TMEM9 NM_001288565.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 28 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288565.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM9	NM_001288565.2	MANE Select	c.366T>C	p.Tyr122Tyr	synonymous	Exon 4 of 5	NP_001275494.1
	TMEM9	NM_001288571.2		c.441T>C	p.Tyr147Tyr	synonymous	Exon 5 of 6	NP_001275500.1
	TMEM9	NM_001288570.2		c.375T>C	p.Tyr125Tyr	synonymous	Exon 5 of 6	NP_001275499.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM9	ENST00000367330.6	TSL:1 MANE Select	c.366T>C	p.Tyr122Tyr	synonymous	Exon 4 of 5	ENSP00000356299.1
	TMEM9	ENST00000367333.6	TSL:1	c.366T>C	p.Tyr122Tyr	synonymous	Exon 5 of 6	ENSP00000356302.2
	TMEM9	ENST00000367334.9	TSL:1	c.366T>C	p.Tyr122Tyr	synonymous	Exon 5 of 6	ENSP00000356303.5

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110605 AN: 151972 Hom.: 40443 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.727

GnomAD2 exomes AF: 0.748 AC: 187870 AN: 251162 AF XY: 0.752

Gnomad AFR exome AF: 0.658

Gnomad AMR exome AF: 0.753

Gnomad ASJ exome AF: 0.748

Gnomad EAS exome AF: 0.634

Gnomad FIN exome AF: 0.787

Gnomad NFE exome AF: 0.771

Gnomad OTH exome AF: 0.747

GnomAD4 exome AF: 0.759 AC: 1108674 AN: 1461590 Hom.: 421569 Cov.: 47 AF XY: 0.759 AC XY: 551712 AN XY: 727104

African (AFR) AF: 0.654 AC: 21896 AN: 33474

American (AMR) AF: 0.747 AC: 33394 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 19519 AN: 26136

East Asian (EAS) AF: 0.656 AC: 26025 AN: 39684

South Asian (SAS) AF: 0.750 AC: 64656 AN: 86250

European-Finnish (FIN) AF: 0.795 AC: 42480 AN: 53408

Middle Eastern (MID) AF: 0.676 AC: 3898 AN: 5766

European-Non Finnish (NFE) AF: 0.766 AC: 851633 AN: 1111788

Other (OTH) AF: 0.748 AC: 45173 AN: 60376

GnomAD4 genome AF: 0.728 AC: 110672 AN: 152090 Hom.: 40465 Cov.: 32 AF XY: 0.727 AC XY: 54016 AN XY: 74328

African (AFR) AF: 0.655 AC: 27178 AN: 41468

American (AMR) AF: 0.721 AC: 11032 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2564 AN: 3470

East Asian (EAS) AF: 0.636 AC: 3274 AN: 5148

South Asian (SAS) AF: 0.740 AC: 3568 AN: 4820

European-Finnish (FIN) AF: 0.787 AC: 8321 AN: 10572

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52430 AN: 67996

Other (OTH) AF: 0.722 AC: 1526 AN: 2114

Alfa AF: 0.756 Hom.: 70365

Bravo AF: 0.719

Asia WGS AF: 0.684 AC: 2379 AN: 3478

EpiCase AF: 0.764

EpiControl AF: 0.758

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.2
DANN	Benign	0.34
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs8158; hg19: chr1-201112981; COSMIC: COSV66243678;