rs750628434

Variant names:

• chr16-19009243-C-G
• rs750628434
• NM_024847.4:c.139C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-19009243-C-G
• chr16-19009243-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024847.4(TMC7):​c.139C>G​(p.Arg47Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. R47Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMC7 NM_024847.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3642686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC7	NM_024847.4	c.139C>G	p.Arg47Gly	missense_variant	Exon 2 of 16	ENST00000304381.10	NP_079123.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC7	ENST00000304381.10	c.139C>G	p.Arg47Gly	missense_variant	Exon 2 of 16	1	NM_024847.4	ENSP00000304710.5
TMC7	ENST00000421369.3	c.-192C>G		5_prime_UTR_variant	Exon 2 of 16	1		ENSP00000397081.3
TMC7	ENST00000569532.5	c.139C>G	p.Arg47Gly	missense_variant	Exon 2 of 15	2		ENSP00000455041.1
TMC7	ENST00000568469.5	n.180C>G		non_coding_transcript_exon_variant	Exon 2 of 10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	0.000014	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	.;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.7	.;L
PhyloP100		1.8
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.16
Sift	Benign	0.034	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		0.28	.;B
Vest4		0.50
MutPred		0.35		Loss of MoRF binding (P = 0.0333);Loss of MoRF binding (P = 0.0333);
MVP		0.47
MPC		0.37
ClinPred		0.92	D
GERP RS		3.2
Varity_R		0.16
gMVP		0.31

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

Other links and lift over

dbSNP: rs750628434; hg19: chr16-19020565;