rs1663742

Variant names:

• chr9-72694227-G-A
• rs1663742
• NM_138691.3:c.65-316G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-72694227-G-A
• chr9-72694227-G-C
• chr9-72694227-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138691.3(TMC1):​c.65-316G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,970 control chromosomes in the GnomAD database, including 21,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (21287 hom., cov: 32)
• Consequence: TMC1 NM_138691.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.17
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 7

  Inheritance: AD, Unknown, AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: SD, AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen
• autosomal dominant nonsyndromic hearing loss 36

  Inheritance: AR, AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-72694227-G-A is Benign according to our data. Variant chr9-72694227-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276260.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138691.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC1	NM_138691.3	MANE Select	c.65-316G>A		intron	N/A	NP_619636.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC1	ENST00000297784.10	TSL:1 MANE Select	c.65-316G>A		intron	N/A	ENSP00000297784.6	Q8TDI8
	TMC1	ENST00000340019.4	TSL:5	c.65-316G>A		intron	N/A	ENSP00000341433.3	Q8TDI8
	TMC1	ENST00000645208.2		c.65-316G>A		intron	N/A	ENSP00000494684.1	Q8TDI8

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77814 AN: 151850 Hom.: 21260 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.423

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: 0.513 AC: 77893 AN: 151970 Hom.: 21287 Cov.: 32 AF XY: 0.510 AC XY: 37878 AN XY: 74252

African (AFR) AF: 0.726 AC: 30097 AN: 41476

American (AMR) AF: 0.462 AC: 7049 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3468

East Asian (EAS) AF: 0.432 AC: 2222 AN: 5144

South Asian (SAS) AF: 0.443 AC: 2141 AN: 4828

European-Finnish (FIN) AF: 0.423 AC: 4464 AN: 10548

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.422 AC: 28656 AN: 67962

Other (OTH) AF: 0.513 AC: 1076 AN: 2096

Alfa AF: 0.307 Hom.: 694

Bravo AF: 0.525

Asia WGS AF: 0.459 AC: 1590 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.018
DANN	Benign	0.55
PhyloP100		-2.2
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: rs1663742; hg19: chr9-75309143;