1-201151825-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001288565.2(TMEM9):c.94A>G(p.Ile32Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM9 NM_001288565.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM9	NM_001288565.2	c.94A>G	p.Ile32Val	missense_variant	2/5	ENST00000367330.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM9	ENST00000367330.6	c.94A>G	p.Ile32Val	missense_variant	2/5	1	NM_001288565.2	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.94A>G (p.I32V) alteration is located in exon 3 (coding exon 2) of the TMEM9 gene. This alteration results from a A to G substitution at nucleotide position 94, causing the isoleucine (I) at amino acid position 32 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	0.0044	T
BayesDel_noAF	Benign	-0.23
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.037	T;T;T;T;T;T;.;.
Eigen	Benign	0.076
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0034	T
MetaRNN	Uncertain	0.45	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	L;L;L;.;L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.60	N;.;N;N;.;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.090	T;.;T;T;.;T;T;T
Sift4G	Uncertain	0.023	D;D;D;D;D;D;D;D
Polyphen		0.064	B;B;B;B;B;.;.;.
Vest4		0.32
MutPred		0.70		.;.;.;Gain of sheet (P = 0.0827);.;.;.;.;
MVP		0.20
MPC		0.41
ClinPred		0.74	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.086
gMVP		0.74

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-201120953;