rs4077833

Variant names:

• chr15-81340342-G-C
• rs4077833
• NM_001080532.3:c.1845-838C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080532.3(TMC3):​c.1845-838C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,026 control chromosomes in the GnomAD database, including 6,318 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (6318 hom., cov: 32)
• Consequence: TMC3 NM_001080532.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC3	NM_001080532.3	c.1845-838C>G		intron_variant	Intron 16 of 21	ENST00000359440.6	NP_001074001.1
TMC3-AS1	NR_120365.1	n.427-1220G>C		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC3	ENST00000359440.6	c.1845-838C>G		intron_variant	Intron 16 of 21	1	NM_001080532.3	ENSP00000352413.5

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33729 AN: 151908 Hom.: 6300 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.222 AC: 33792 AN: 152026 Hom.: 6318 Cov.: 32 AF XY: 0.218 AC XY: 16169 AN XY: 74322

African (AFR) AF: 0.516 AC: 21382 AN: 41404

American (AMR) AF: 0.112 AC: 1713 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1340 AN: 5182

South Asian (SAS) AF: 0.130 AC: 624 AN: 4814

European-Finnish (FIN) AF: 0.0763 AC: 807 AN: 10570

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6875 AN: 67992

Other (OTH) AF: 0.202 AC: 427 AN: 2110

Alfa AF: 0.165 Hom.: 551

Bravo AF: 0.241

Asia WGS AF: 0.202 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.075
DANN	Benign	0.52
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs4077833; hg19: chr15-81632683;