16-18984088-C-T

Position:

• chr16-18984088-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024847.4(TMC7):​c.25C>T​(p.Leu9Phe) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMC7 NM_024847.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.544

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061210185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMC7	NM_024847.4	c.25C>T	p.Leu9Phe	missense_variant	1/16	ENST00000304381.10	NP_079123.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMC7	ENST00000304381.10	c.25C>T	p.Leu9Phe	missense_variant	1/16	1	NM_024847.4	ENSP00000304710.5
TMC7	ENST00000569532.5	c.25C>T	p.Leu9Phe	missense_variant	1/15	2		ENSP00000455041.1
TMC7	ENST00000568469.5	n.66C>T		non_coding_transcript_exon_variant	1/10	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1350998 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 666342

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.25C>T (p.L9F) alteration is located in exon 1 (coding exon 1) of the TMC7 gene. This alteration results from a C to T substitution at nucleotide position 25, causing the leucine (L) at amino acid position 9 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	0.063
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.89
DEOGEN2	Benign	0.0024	.;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.39	T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	.;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.47	N;N
REVEL	Benign	0.12
Sift	Benign	0.23	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.23	.;B
Vest4		0.047
MutPred		0.079		Gain of glycosylation at S7 (P = 0.1446);Gain of glycosylation at S7 (P = 0.1446);
MVP		0.34
MPC		0.30
ClinPred		0.12	T
GERP RS		1.1
Varity_R		0.057
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-18995410;