rs4077833

Positions:

• chr15-81340342-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359440.6(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 ENST00000359440.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
TMC3	NM_001080532.3	c.1845-838C>G		intron_variant		ENST00000359440.6	NP_001074001.1
TMC3-AS1	NR_120365.1	n.427-1220G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMC3	ENST00000359440.6	c.1845-838C>G		intron_variant		1	NM_001080532.3	ENSP00000352413	P4
TMC3-AS1	ENST00000560851.2	n.311-1220G>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0763

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.202

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

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: rs4077833; hg19: chr15-81632683;