Variant chr16-19021739-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_024847.4(TMC7):c.571C>T(p.Leu191Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,461,872 control chromosomes in the GnomAD database, including 1 homozygotes. 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: not found (cov: 32)

Exomes 𝑓: 0.000030 ( 1 hom. )

Consequence

TMC7
NM_024847.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

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:

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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=0.068986684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMC7	NM_024847.4 linkuse as main transcript	c.571C>T	p.Leu191Phe	missense_variant	4/16	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.571C>T	p.Leu191Phe	missense_variant	4/16	1	NM_024847.4	ENSP00000304710.5	Q7Z402-1
TMC7	ENST00000421369.3 linkuse as main transcript	c.241C>T	p.Leu81Phe	missense_variant	4/16	1		ENSP00000397081.3	Q7Z402-2
TMC7	ENST00000569532.5 linkuse as main transcript	c.571C>T	p.Leu191Phe	missense_variant	4/15	2		ENSP00000455041.1	H3BNW8
TMC7	ENST00000568469.5 linkuse as main transcript	n.612C>T		non_coding_transcript_exon_variant	4/10	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000994

AC:

AN:

251410

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135880

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:

0.000719

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727234

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:

0.000394

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.000123

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

Jan 02, 2024

The c.571C>T (p.L191F) alteration is located in exon 4 (coding exon 4) of the TMC7 gene. This alteration results from a C to T substitution at nucleotide position 571, causing the leucine (L) at amino acid position 191 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

0.095

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

0.028

Eigen_PC

Benign

-0.017

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.069

T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

2.0

.;M;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.058

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.38

.;B;.

Vest4

0.18

MutPred

0.41

Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);.;

MVP

0.28

MPC

0.29

ClinPred

0.079

GERP RS

4.0

Varity_R

0.086

gMVP

0.67

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