rs10485603

Variant names:

• chr20-2614869-T-C
• rs10485603
• NM_080751.3:c.1873-1268T>C

Variant summary

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

The NM_080751.3(TMC2):​c.1873-1268T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,018 control chromosomes in the GnomAD database, including 1,567 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 0.13 (1567 hom., cov: 32)
• Consequence: TMC2 NM_080751.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 3 publications found

Genes affected

TMC2 (HGNC:16527): (transmembrane channel like 2) This gene encodes a transmembrane protein that is necesssary for mechanotransduction in cochlear hair cells of the inner ear. Mutations in this gene may underlie hereditary disorders of balance and hearing. [provided by RefSeq, Aug 2015]

LOC105372505 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC2	NM_080751.3	c.1873-1268T>C		intron_variant	Intron 14 of 19	ENST00000358864.2	NP_542789.2
TMC2	XM_005260660.5	c.1948-1268T>C		intron_variant	Intron 12 of 17		XP_005260717.1
TMC2	XR_001754152.2	n.2779+849T>C		intron_variant	Intron 12 of 12
LOC105372505	XR_007067502.1	n.938-737A>G		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC2	ENST00000358864.2	c.1873-1268T>C		intron_variant	Intron 14 of 19	1	NM_080751.3	ENSP00000351732.1
TMC2	ENST00000496948.2	n.*572+849T>C		intron_variant	Intron 4 of 5	2		ENSP00000495303.1
TMC2	ENST00000644205.1	n.2123+849T>C		intron_variant	Intron 13 of 14

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19190 AN: 151900 Hom.: 1570 Cov.: 32

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.126 AC: 19180 AN: 152018 Hom.: 1567 Cov.: 32 AF XY: 0.124 AC XY: 9234 AN XY: 74360

African (AFR) AF: 0.0346 AC: 1438 AN: 41512

American (AMR) AF: 0.141 AC: 2148 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3468

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5180

South Asian (SAS) AF: 0.113 AC: 543 AN: 4824

European-Finnish (FIN) AF: 0.156 AC: 1630 AN: 10466

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11996 AN: 67966

Other (OTH) AF: 0.145 AC: 307 AN: 2110

Alfa AF: 0.169 Hom.: 2614

Bravo AF: 0.122

Asia WGS AF: 0.0620 AC: 215 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.097
DANN	Benign	0.58
PhyloP100		-1.2
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: rs10485603; hg19: chr20-2595515;