Variant 9-72578000-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_138691.3(TMC1):c.-329C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,120 control chromosomes in the GnomAD database, including 1,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 1877 hom., cov: 31)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

TMC1
NM_138691.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.299

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 9-72578000-C-A is Benign according to our data. Variant chr9-72578000-C-A is described in ClinVar as [Benign]. Clinvar id is 367247.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC1	NM_138691.3 linkuse as main transcript	c.-329C>A		5_prime_UTR_variant	2/24	ENST00000297784.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC1	ENST00000297784.10 linkuse as main transcript	c.-329C>A		5_prime_UTR_variant	2/24	1	NM_138691.3	P2

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20348

AN:

151898

Hom.:

1859

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0947

Gnomad ASJ

AF:

0.0850

Gnomad EAS

AF:

0.0234

Gnomad SAS

AF:

0.0434

Gnomad FIN

AF:

0.0539

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.125

GnomAD4 exome

AF:

0.125

AC:

AN:

104

Hom.:

Cov.:

AF XY:

0.134

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.333

Gnomad4 AMR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.134

AC:

20396

AN:

152016

Hom.:

1877

Cov.:

AF XY:

0.130

AC XY:

9667

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.245

Gnomad4 AMR

AF:

0.0944

Gnomad4 ASJ

AF:

0.0850

Gnomad4 EAS

AF:

0.0234

Gnomad4 SAS

AF:

0.0434

Gnomad4 FIN

AF:

0.0539

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.123

Alfa

AF:

0.0604

Hom.:

Bravo

AF:

0.143

Asia WGS

AF:

0.0460

AC:

161

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 36

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal recessive nonsyndromic hearing loss 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

Cadd

Benign

1.8

Dann

Benign

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over