rs200892782

Variant names:

• chr15-81332858-T-A
• rs200892782
• NM_001080532.3:c.2864A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-81332858-T-A
• chr15-81332858-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080532.3(TMC3):​c.2864A>T​(p.Lys955Ile) 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: 32)
• Consequence: TMC3 NM_001080532.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394

Genes affected

TMC3 (HGNC:22995): (transmembrane channel like 3) 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]

TMC3-AS1 (HGNC:51424): (TMC3 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13005966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC3	NM_001080532.3	c.2864A>T	p.Lys955Ile	missense_variant	Exon 22 of 22	ENST00000359440.6	NP_001074001.1
TMC3-AS1	NR_120365.1	n.426+317T>A		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC3	ENST00000359440.6	c.2864A>T	p.Lys955Ile	missense_variant	Exon 22 of 22	1	NM_001080532.3	ENSP00000352413.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 81

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.61
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	.;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.10
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.027	D;D
Polyphen		0.64	.;P
Vest4		0.15
MutPred		0.31		.;Loss of ubiquitination at K955 (P = 0.0047);
MVP		0.42
MPC		0.41
ClinPred		0.67	D
GERP RS		-4.1
Varity_R		0.12
gMVP		0.10

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

LitVar

Other links and lift over

dbSNP: rs200892782; hg19: chr15-81625199;