chr9-72694930-T-C

Position:

• chr9-72694930-T-C

Variant summary

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

The NM_138691.3(TMC1):​c.236+216T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,942 control chromosomes in the GnomAD database, including 21,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (21258 hom., cov: 32)
• Consequence: TMC1 NM_138691.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

Genes affected

TMC1 (HGNC:16513): (transmembrane channel like 1) This gene is considered a member of a gene family predicted to encode transmembrane proteins. The specific function of this gene is unknown; however, it is known to be required for normal function of cochlear hair cells. Mutations in this gene have been associated with progressive postlingual hearing loss and profound prelingual deafness. [provided by RefSeq, Jul 2008]

TMC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMC1	NM_138691.3	c.236+216T>C		intron_variant		ENST00000297784.10	NP_619636.2
TMC1	XM_017014256.2	c.239+216T>C		intron_variant			XP_016869745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMC1	ENST00000297784.10	c.236+216T>C		intron_variant		1	NM_138691.3	ENSP00000297784.6

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77753 AN: 151824 Hom.: 21231 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.512 AC: 77832 AN: 151942 Hom.: 21258 Cov.: 32 AF XY: 0.510 AC XY: 37845 AN XY: 74264

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.513

Alfa AF: 0.467 Hom.: 2068

Bravo AF: 0.525

Asia WGS AF: 0.458 AC: 1583 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.81

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: rs2589614; hg19: chr9-75309846; COSMIC: COSV52771171;