chr1-201143853-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001288565.2(TMEM9):​c.366T>G​(p.Tyr122*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM9 NM_001288565.2 stop_gained
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>G	p.Tyr122*	stop_gained	Exon 4 of 5	NP_001275494.1
	TMEM9	NM_001288571.2		c.441T>G	p.Tyr147*	stop_gained	Exon 5 of 6	NP_001275500.1
	TMEM9	NM_001288570.2		c.375T>G	p.Tyr125*	stop_gained	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>G	p.Tyr122*	stop_gained	Exon 4 of 5	ENSP00000356299.1
	TMEM9	ENST00000367333.6	TSL:1	c.366T>G	p.Tyr122*	stop_gained	Exon 5 of 6	ENSP00000356302.2
	TMEM9	ENST00000367334.9	TSL:1	c.366T>G	p.Tyr122*	stop_gained	Exon 5 of 6	ENSP00000356303.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 70365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.073
FATHMM_MKL	Uncertain	0.83	D
PhyloP100		1.1
Vest4		0.46
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=14/186	disease causing

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;