Genetic Variant TMC1:c.236+511T>C (chr9-72695225-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138691.3(TMC1):c.236+511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,992 control chromosomes in the GnomAD database, including 25,655 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 0.57 ( 25655 hom., cov: 31)

Consequence

TMC1
NM_138691.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.77

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC1	NM_138691.3 link	c.236+511T>C		intron_variant	Intron 7 of 23	ENST00000297784.10	NP_619636.2	Q8TDI8
TMC1	XM_017014256.2 link	c.239+511T>C		intron_variant	Intron 4 of 20		XP_016869745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC1	ENST00000297784.10 link	c.236+511T>C		intron_variant	Intron 7 of 23	1	NM_138691.3	ENSP00000297784.6		Q8TDI8

Frequencies

GnomAD3 genomes

AF:

0.565

AC:

85848

AN:

151874

Hom.:

25610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.773

Gnomad AMI

AF:

0.516

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.566

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

GnomAD4 genome

AF:

0.565

AC:

85948

AN:

151992

Hom.:

25655

Cov.:

AF XY:

0.562

AC XY:

41741

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.773

Gnomad4 AMR

AF:

0.513

Gnomad4 ASJ

AF:

0.545

Gnomad4 EAS

AF:

0.451

Gnomad4 SAS

AF:

0.467

Gnomad4 FIN

AF:

0.460

Gnomad4 NFE

AF:

0.484

Gnomad4 OTH

AF:

0.566

Alfa

AF:

0.522

Hom.:

2532

Bravo

AF:

0.581

Asia WGS

AF:

0.481

AC:

1670

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

5.6

DANN

Benign

0.68

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over