Variant chr4-82485656-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001080506.3(TMEM150C):c.605T>C(p.Met202Thr) variant causes a missense change involving the alteration of a 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: 31)

Consequence

TMEM150C
NM_001080506.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.19

Variant links:

Genes affected

TMEM150C (HGNC:37263): (transmembrane protein 150C) This gene encodes a transmembrane protein component of a mechanosensitve ion channel that is activated by mechanical stimuli in various cell types and confers slowly adapting, mechanically activated currents in dorsal root ganglion neurons. Mechanically activated ion channels are sensors that are critical for hearing, touch, pain, and blood pressure regulation. [provided by RefSeq, Jul 2017]

TMEM150C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM150C	NM_001080506.3 linkuse as main transcript	c.605T>C	p.Met202Thr	missense_variant	8/8	ENST00000449862.7	NP_001073975.1	B9EJG8-1
TMEM150C	NM_001353454.2 linkuse as main transcript	c.695T>C	p.Met232Thr	missense_variant	8/8		NP_001340383.1
TMEM150C	NM_001353455.2 linkuse as main transcript	c.423-25T>C		intron_variant			NP_001340384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM150C	ENST00000449862.7 linkuse as main transcript	c.605T>C	p.Met202Thr	missense_variant	8/8	1	NM_001080506.3	ENSP00000403438.2		B9EJG8-1
TMEM150C	ENST00000515780.6 linkuse as main transcript	c.605T>C	p.Met202Thr	missense_variant	8/8	2		ENSP00000420919.1		B9EJG8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000415

AC:

AN:

241114

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130484

show subpopulations

Gnomad AFR exome

AF:

0.0000686

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2024

The c.605T>C (p.M202T) alteration is located in exon 8 (coding exon 7) of the TMEM150C gene. This alteration results from a T to C substitution at nucleotide position 605, causing the methionine (M) at amino acid position 202 to be replaced by a threonine (T). 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

Pathogenic

0.78

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.53

D;D

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.044

MetaRNN

Pathogenic

0.85

D;D

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.9

D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.0050

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.97

D;D

Vest4

0.84

MutPred

0.63

Gain of catalytic residue at M202 (P = 0.1679);Gain of catalytic residue at M202 (P = 0.1679);

MVP

0.63

MPC

1.4

ClinPred

0.90

GERP RS

5.4

Varity_R

0.50

gMVP

0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over