NM_001080532.3:c.2459+336C>T

Variant names:

• chr15-81334384-G-A
• rs3935740
• NM_001080532.3:c.2459+336C>T

Variant summary

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

The NM_001080532.3(TMC3):​c.2459+336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,086 control chromosomes in the GnomAD database, including 6,027 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 0.21 (6027 hom., cov: 32)
• Consequence: TMC3 NM_001080532.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC3	NM_001080532.3	c.2459+336C>T		intron_variant	Intron 21 of 21	ENST00000359440.6	NP_001074001.1
TMC3-AS1	NR_120365.1	n.426+1843G>A		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC3	ENST00000359440.6	c.2459+336C>T		intron_variant	Intron 21 of 21	1	NM_001080532.3	ENSP00000352413.5

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32370 AN: 151968 Hom.: 6009 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0890

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.213 AC: 32434 AN: 152086 Hom.: 6027 Cov.: 32 AF XY: 0.209 AC XY: 15529 AN XY: 74376

African (AFR) AF: 0.509 AC: 21088 AN: 41438

American (AMR) AF: 0.110 AC: 1681 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1304 AN: 5162

South Asian (SAS) AF: 0.118 AC: 566 AN: 4814

European-Finnish (FIN) AF: 0.0690 AC: 732 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0890 AC: 6049 AN: 67996

Other (OTH) AF: 0.196 AC: 415 AN: 2112

Alfa AF: 0.130 Hom.: 3950

Bravo AF: 0.233

Asia WGS AF: 0.194 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.50
DANN	Benign	0.27
PhyloP100		-0.0020
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: rs3935740; hg19: chr15-81626725;