rs3935740

Positions:

• chr15-81334384-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
TMC3	NM_001080532.3	c.2459+336C>T		intron_variant		ENST00000359440.6
TMC3-AS1	NR_120365.1	n.426+1843G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC3	ENST00000359440.6	c.2459+336C>T		intron_variant		1	NM_001080532.3	P4
TMC3-AS1	ENST00000560851.2	n.310+1843G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0690

Gnomad4 NFE AF: 0.0890

Gnomad4 OTH AF: 0.196

Alfa AF: 0.114 Hom.: 1998

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

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: rs3935740; hg19: chr15-81626725;