Genetic Variant NM_024847.4:c.38G>C (chr16-18984101-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024847.4(TMC7):c.38G>C(p.Arg13Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 1,351,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R13K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TMC7
NM_024847.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.21

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08664316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC7	NM_024847.4 link	c.38G>C	p.Arg13Thr	missense_variant	Exon 1 of 16	ENST00000304381.10	NP_079123.3	Q7Z402-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMC7	ENST00000304381.10 link	c.38G>C	p.Arg13Thr	missense_variant	Exon 1 of 16	1	NM_024847.4	ENSP00000304710.5	Q7Z402-1
TMC7	ENST00000569532.5 link	c.38G>C	p.Arg13Thr	missense_variant	Exon 1 of 15	2		ENSP00000455041.1	H3BNW8
TMC7	ENST00000568469.5 link	n.79G>C		non_coding_transcript_exon_variant	Exon 1 of 10	2
TMC7	ENST00000421369.3 link	c.-744G>C		upstream_gene_variant		1		ENSP00000397081.3	Q7Z402-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000133

AC:

AN:

1351070

Hom.:

Cov.:

AF XY:

0.0000150

AC XY:

AN XY:

666336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27546

American (AMR)

AF:

0.00

AC:

AN:

32272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24040

East Asian (EAS)

AF:

0.00

AC:

AN:

31838

South Asian (SAS)

AF:

0.00

AC:

AN:

75698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3966

European-Non Finnish (NFE)

AF:

0.0000159

AC:

AN:

1066162

Other (OTH)

AF:

0.0000178

AC:

AN:

56296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.0018

.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.80

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.087

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.69

.;N

PhyloP100

2.2

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.090

N;N

REVEL

Benign

0.13

Sift

Benign

0.056

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.079

.;B

Vest4

0.22

MutPred

0.093

Gain of phosphorylation at R13 (P = 0.033);Gain of phosphorylation at R13 (P = 0.033);

MVP

0.34

MPC

0.38

ClinPred

0.16

GERP RS

2.3

PromoterAI

-0.34

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.37

Mutation Taster

=89/11

polymorphism

(source)

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

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NM_024847.4:c.38G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over