Variant 4-82504636-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080506.3(TMEM150C):c.22G>A(p.Val8Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000319 in 1,613,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

TMEM150C
NM_001080506.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10319579).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM150C	NM_001080506.3 linkuse as main transcript	c.22G>A	p.Val8Ile	missense_variant	2/8	ENST00000449862.7	NP_001073975.1	B9EJG8-1
TMEM150C	NM_001353454.2 linkuse as main transcript	c.112G>A	p.Val38Ile	missense_variant	2/8		NP_001340383.1
TMEM150C	NM_001353455.2 linkuse as main transcript	c.22G>A	p.Val8Ile	missense_variant	2/8		NP_001340384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM150C	ENST00000449862.7 linkuse as main transcript	c.22G>A	p.Val8Ile	missense_variant	2/8	1	NM_001080506.3	ENSP00000403438.2	B9EJG8-1
TMEM150C	ENST00000515780.6 linkuse as main transcript	c.22G>A	p.Val8Ile	missense_variant	2/8	2		ENSP00000420919.1	B9EJG8-1
TMEM150C	ENST00000508701.5 linkuse as main transcript	c.22G>A	p.Val8Ile	missense_variant	2/7	4		ENSP00000421812.1	D6RAQ9
TMEM150C	ENST00000454948.3 linkuse as main transcript	c.22G>A	p.Val8Ile	missense_variant	3/6	4		ENSP00000414988.3	D6RDW6

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000133

AC:

AN:

248762

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

134958

show subpopulations

Gnomad AFR exome

AF:

0.000388

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000334

AC:

488

AN:

1461374

Hom.:

Cov.:

AF XY:

0.000321

AC XY:

233

AN XY:

726954

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000402

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000177

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000183

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000262

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.0000745

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000534

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

May 02, 2024

The c.22G>A (p.V8I) alteration is located in exon 2 (coding exon 1) of the TMEM150C gene. This alteration results from a G to A substitution at nucleotide position 22, causing the valine (V) at amino acid position 8 to be replaced by an isoleucine (I). 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

0.075

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.011

T;T;.;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.67

.;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;L;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.10

N;N;N;N

REVEL

Benign

0.040

Sift

Benign

0.43

T;T;T;T

Sift4G

Benign

0.28

T;T;T;.

Polyphen

0.88

P;P;.;.

Vest4

0.23

MVP

0.061

MPC

0.40

ClinPred

0.023

GERP RS

4.1

Varity_R

0.026

gMVP

0.44

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