11-66295004-T-C

Position:

• chr11-66295004-T-C

Variant summary

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

The NM_153266.4(TMEM151A):​c.758T>C​(p.Leu253Pro) variant causes a missense change. 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: TMEM151A NM_153266.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.04

Genes affected

TMEM151A (HGNC:28497): (transmembrane protein 151A) Predicted to be integral component of 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 11-66295004-T-C is Pathogenic according to our data. Variant chr11-66295004-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 2443873.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM151A	NM_153266.4	c.758T>C	p.Leu253Pro	missense_variant	2/2	ENST00000327259.5	NP_694998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM151A	ENST00000327259.5	c.758T>C	p.Leu253Pro	missense_variant	2/2	1	NM_153266.4	ENSP00000326244	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Episodic kinesigenic dyskinesia 3 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.76
MutPred		0.57		Loss of helix (P = 0.028);
MVP		0.12
ClinPred		0.97	D
GERP RS		4.2
Varity_R		0.90
gMVP		0.97

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: chr11-66062475;