Variant chr4-82504638-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001080506.3(TMEM150C):c.20G>A(p.Ser7Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000014 ( 0 hom. )

Consequence

TMEM150C
NM_001080506.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2788343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM150C	NM_001080506.3 linkuse as main transcript	c.20G>A	p.Ser7Asn	missense_variant	2/8	ENST00000449862.7	NP_001073975.1	B9EJG8-1
TMEM150C	NM_001353454.2 linkuse as main transcript	c.110G>A	p.Ser37Asn	missense_variant	2/8		NP_001340383.1
TMEM150C	NM_001353455.2 linkuse as main transcript	c.20G>A	p.Ser7Asn	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.20G>A	p.Ser7Asn	missense_variant	2/8	1	NM_001080506.3	ENSP00000403438.2	B9EJG8-1
TMEM150C	ENST00000515780.6 linkuse as main transcript	c.20G>A	p.Ser7Asn	missense_variant	2/8	2		ENSP00000420919.1	B9EJG8-1
TMEM150C	ENST00000508701.5 linkuse as main transcript	c.20G>A	p.Ser7Asn	missense_variant	2/7	4		ENSP00000421812.1	D6RAQ9
TMEM150C	ENST00000454948.3 linkuse as main transcript	c.20G>A	p.Ser7Asn	missense_variant	3/6	4		ENSP00000414988.3	D6RDW6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461402

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Oct 01, 2024

The c.20G>A (p.S7N) 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 20, causing the serine (S) at amino acid position 7 to be replaced by an asparagine (N). 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

Uncertain

0.50

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.026

T;T;.;.

Eigen

Benign

-0.0097

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

.;T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L;.;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.067

Sift

Uncertain

0.011

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;.

Polyphen

0.084

B;B;.;.

Vest4

0.49

MutPred

0.49

Gain of catalytic residue at S7 (P = 0.087);Gain of catalytic residue at S7 (P = 0.087);Gain of catalytic residue at S7 (P = 0.087);Gain of catalytic residue at S7 (P = 0.087);

MVP

0.30

MPC

0.98

ClinPred

0.83

GERP RS

5.0

Varity_R

0.17

gMVP

0.82

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