16-18984110-G-T

Variant names:

• chr16-18984110-G-T
• rs777003939
• NM_024847.4:c.47G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024847.4(TMC7):​c.47G>T​(p.Arg16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000074 in 1,350,620 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. R16Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: TMC7 NM_024847.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.878
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07925612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC7	NM_024847.4	c.47G>T	p.Arg16Leu	missense_variant	Exon 1 of 16	ENST00000304381.10	NP_079123.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC7	ENST00000304381.10	c.47G>T	p.Arg16Leu	missense_variant	Exon 1 of 16	1	NM_024847.4	ENSP00000304710.5
TMC7	ENST00000569532.5	c.47G>T	p.Arg16Leu	missense_variant	Exon 1 of 15	2		ENSP00000455041.1
TMC7	ENST00000568469.5	n.88G>T		non_coding_transcript_exon_variant	Exon 1 of 10	2
TMC7	ENST00000421369.3	c.-735G>T		upstream_gene_variant		1		ENSP00000397081.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.40e-7 AC: 1 AN: 1350620 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 666102

African (AFR) AF: 0.00 AC: 0 AN: 27546

American (AMR) AF: 0.00 AC: 0 AN: 32184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24010

East Asian (EAS) AF: 0.00 AC: 0 AN: 31802

South Asian (SAS) AF: 0.00 AC: 0 AN: 75640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3964

European-Non Finnish (NFE) AF: 9.38e-7 AC: 1 AN: 1065924

Other (OTH) AF: 0.00 AC: 0 AN: 56296

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.66
DEOGEN2	Benign	0.0047	.;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	.;L
PhyloP100		0.88
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.028	D;T
Sift4G	Benign	0.064	T;T
Polyphen		0.0	.;B
Vest4		0.21
MutPred		0.11		Loss of glycosylation at P14 (P = 0.2116);Loss of glycosylation at P14 (P = 0.2116);
MVP		0.26
MPC		0.32
ClinPred		0.080	T
GERP RS		0.95
PromoterAI		-0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.15
gMVP		0.49

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: rs777003939; hg19: chr16-18995432;