4-82504612-A-G

Position:

• chr4-82504612-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080506.3(TMEM150C):​c.46T>C​(p.Phe16Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM150C NM_001080506.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.53

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]

ACMG classification

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=0.15580201).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM150C	NM_001080506.3	c.46T>C	p.Phe16Leu	missense_variant	2/8	ENST00000449862.7	NP_001073975.1
TMEM150C	NM_001353454.2	c.136T>C	p.Phe46Leu	missense_variant	2/8		NP_001340383.1
TMEM150C	NM_001353455.2	c.46T>C	p.Phe16Leu	missense_variant	2/8		NP_001340384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM150C	ENST00000449862.7	c.46T>C	p.Phe16Leu	missense_variant	2/8	1	NM_001080506.3	ENSP00000403438.2
TMEM150C	ENST00000515780.6	c.46T>C	p.Phe16Leu	missense_variant	2/8	2		ENSP00000420919.1
TMEM150C	ENST00000508701.5	c.46T>C	p.Phe16Leu	missense_variant	2/7	4		ENSP00000421812.1
TMEM150C	ENST00000454948.3	c.46T>C	p.Phe16Leu	missense_variant	3/6	4		ENSP00000414988.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461422 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726960

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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 Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 07, 2022

The c.46T>C (p.F16L) alteration is located in exon 2 (coding exon 1) of the TMEM150C gene. This alteration results from a T to C substitution at nucleotide position 46, causing the phenylalanine (F) at amino acid position 16 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	Pathogenic	0.77
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T;.;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	.;T;T;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.41	N;N;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	2.2	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.29	T;T;T;.
Polyphen		0.0	B;B;.;.
Vest4		0.58
MutPred		0.51		Loss of catalytic residue at F16 (P = 0.2449);Loss of catalytic residue at F16 (P = 0.2449);Loss of catalytic residue at F16 (P = 0.2449);Loss of catalytic residue at F16 (P = 0.2449);
MVP		0.15
MPC		0.49
ClinPred		0.75	D
GERP RS		5.8
Varity_R		0.092
gMVP		0.77

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: chr4-83425765;