2-134550591-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_030923.5(TMEM163):c.437A>G(p.His146Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM163 NM_030923.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.65

Genes affected

TMEM163 (HGNC:25380): (transmembrane protein 163) Predicted to enable zinc ion binding activity. Predicted to be involved in zinc ion import into synaptic vesicle. Predicted to be located in early endosome membrane. Predicted to be active in intracellular vesicle and plasma membrane. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-134550591-T-C is Pathogenic according to our data. Variant chr2-134550591-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 2443752.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM163	NM_030923.5	c.437A>G	p.His146Arg	missense_variant	4/8	ENST00000281924.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM163	ENST00000281924.6	c.437A>G	p.His146Arg	missense_variant	4/8	1	NM_030923.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Leukodystrophy, hypomyelinating, 25 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.41
Sift	Benign	0.099	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.44		Gain of MoRF binding (P = 0.0659);
MVP		0.51
MPC		1.7
ClinPred		0.90	D
GERP RS		5.6
Varity_R		0.18
gMVP		0.90

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: chr2-135308162;