Variant 16-19016518-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024847.4(TMC7):c.380C>T(p.Ser127Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000527 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

TMC7
NM_024847.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64

Variant links:

Genes affected

TMC7 (HGNC:23000): (transmembrane channel like 7) Predicted to enable mechanosensitive ion channel activity. Predicted to be involved in ion transmembrane transport. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMC7 links:

TMC7 (HGNC:):

TMC7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMC7	NM_024847.4 linkuse as main transcript	c.380C>T	p.Ser127Phe	missense_variant	3/16	ENST00000304381.10	NP_079123.3	Q7Z402-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMC7	ENST00000304381.10 linkuse as main transcript	c.380C>T	p.Ser127Phe	missense_variant	3/16	1	NM_024847.4	ENSP00000304710.5	Q7Z402-1
TMC7	ENST00000421369.3 linkuse as main transcript	c.50C>T	p.Ser17Phe	missense_variant	3/16	1		ENSP00000397081.3	Q7Z402-2
TMC7	ENST00000569532.5 linkuse as main transcript	c.380C>T	p.Ser127Phe	missense_variant	3/15	2		ENSP00000455041.1	H3BNW8
TMC7	ENST00000568469.5 linkuse as main transcript	n.421C>T		non_coding_transcript_exon_variant	3/10	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

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:

0.0000278

AC:

AN:

251446

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135908

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000575

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

727242

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000728

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74346

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

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000151

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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, 2021

The c.380C>T (p.S127F) alteration is located in exon 3 (coding exon 3) of the TMC7 gene. This alteration results from a C to T substitution at nucleotide position 380, causing the serine (S) at amino acid position 127 to be replaced by a phenylalanine (F). 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

0.28

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0075

.;T;.

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.52

D;D;D

MetaSVM

Benign

-0.44

MutationAssessor

Benign

2.0

.;M;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.0

N;N;N

REVEL

Uncertain

0.35

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.54

T;T;T

Polyphen

0.11

.;B;.

Vest4

0.86

MutPred

0.48

Loss of disorder (P = 0.0116);Loss of disorder (P = 0.0116);.;

MVP

0.36

MPC

0.50

ClinPred

0.37

GERP RS

5.5

Varity_R

0.24

gMVP

0.70

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