4-82504636-C-G

Position:

chr4-82504636-C-G

Variant summary

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

The NM_001080506.3(TMEM150C):c.22G>C(p.Val8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,550 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 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=0.18486142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM150C	NM_001080506.3 linkuse as main transcript	c.22G>C	p.Val8Leu	missense_variant	2/8	ENST00000449862.7	NP_001073975.1	B9EJG8-1
TMEM150C	NM_001353454.2 linkuse as main transcript	c.112G>C	p.Val38Leu	missense_variant	2/8		NP_001340383.1
TMEM150C	NM_001353455.2 linkuse as main transcript	c.22G>C	p.Val8Leu	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>C	p.Val8Leu	missense_variant	2/8	1	NM_001080506.3	ENSP00000403438.2	B9EJG8-1
TMEM150C	ENST00000515780.6 linkuse as main transcript	c.22G>C	p.Val8Leu	missense_variant	2/8	2		ENSP00000420919.1	B9EJG8-1
TMEM150C	ENST00000508701.5 linkuse as main transcript	c.22G>C	p.Val8Leu	missense_variant	2/7	4		ENSP00000421812.1	D6RAQ9
TMEM150C	ENST00000454948.3 linkuse as main transcript	c.22G>C	p.Val8Leu	missense_variant	3/6	4		ENSP00000414988.3	D6RDW6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000804

AC:

AN:

248762

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134958

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461380

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726958

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

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

Nov 25, 2024

The c.22G>C (p.V8L) alteration is located in exon 2 (coding exon 1) of the TMEM150C gene. This alteration results from a G to C substitution at nucleotide position 22, causing the valine (V) at amino acid position 8 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.42

CADD

Benign

4.5

DANN

Benign

0.96

DEOGEN2

Benign

0.010

T;T;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.79

.;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.58

N;N;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.44

N;N;N;N

REVEL

Benign

0.087

Sift

Benign

0.46

T;T;T;T

Sift4G

Benign

0.26

T;T;T;.

Polyphen

0.77

P;P;.;.

Vest4

0.47

MutPred

0.45

Loss of methylation at K4 (P = 0.0845);Loss of methylation at K4 (P = 0.0845);Loss of methylation at K4 (P = 0.0845);Loss of methylation at K4 (P = 0.0845);

MVP

0.14

MPC

0.41

ClinPred

0.073

GERP RS

4.1

Varity_R

0.043

gMVP

0.69

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