chr16-18984088-C-T

Variant names:

• chr16-18984088-C-T
• NM_024847.4:c.25C>T

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• 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: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024847.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC7	NM_024847.4	MANE Select	c.25C>T	p.Leu9Phe	missense	Exon 1 of 16	NP_079123.3	Q7Z402-1
	TMC7	NM_001300732.2		c.25C>T	p.Leu9Phe	missense	Exon 1 of 15	NP_001287661.1	H3BNW8
	TMC7	NM_001324265.1		c.25C>T	p.Leu9Phe	missense	Exon 1 of 15	NP_001311194.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC7	ENST00000304381.10	TSL:1 MANE Select	c.25C>T	p.Leu9Phe	missense	Exon 1 of 16	ENSP00000304710.5	Q7Z402-1
	TMC7	ENST00000569532.5	TSL:2	c.25C>T	p.Leu9Phe	missense	Exon 1 of 15	ENSP00000455041.1	H3BNW8
	TMC7	ENST00000931979.1		c.25C>T	p.Leu9Phe	missense	Exon 1 of 17	ENSP00000602038.1

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

African (AFR) AF: 0.00 AC: 0 AN: 27512

American (AMR) AF: 0.00 AC: 0 AN: 32260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24020

East Asian (EAS) AF: 0.00 AC: 0 AN: 31826

South Asian (SAS) AF: 0.00 AC: 0 AN: 75712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3968

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1066172

Other (OTH) AF: 0.00 AC: 0 AN: 56276

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.54
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.47	N
REVEL	Benign	0.12
Sift	Benign	0.23	T
Sift4G	Benign	0.29	T
Polyphen		0.23	B
Vest4		0.047
MutPred		0.079		Gain of glycosylation at S7 (P = 0.1446)
MVP		0.34
MPC		0.30
ClinPred		0.12	T
GERP RS		1.1
PromoterAI		0.14	Neutral
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

Other links and lift over

hg19: chr16-18995410;