rs77829267

Variant names:

• chr3-46701033-C-A
• rs77829267
• NM_001370524.1:c.-66-4757C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-46701033-C-A
• chr3-46701033-C-G
• chr3-46701033-C-T

Variant summary

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

The NM_001370524.1(TMIE):​c.-66-4757C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 147,950 control chromosomes in the GnomAD database, including 783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.096 (783 hom., cov: 30)
• Consequence: TMIE NM_001370524.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.439
• Publications: 2 publications found

Genes affected

TMIE (HGNC:30800): (transmembrane inner ear) This gene encodes a transmembrane inner ear protein. Studies in mouse suggest that this gene is required for normal postnatal maturation of sensory hair cells in the cochlea, including correct development of stereocilia bundles. This gene is one of multiple genes responsible for recessive non-syndromic deafness (DFNB), also known as autosomal recessive nonsyndromic hearing loss (ARNSHL), the most common form of congenitally acquired inherited hearing impairment. [provided by RefSeq, Mar 2009]

TMIE Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 6

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.74).
• BP6: Variant 3-46701033-C-A is Benign according to our data. Variant chr3-46701033-C-A is described in ClinVar as Benign. ClinVar VariationId is 1258770.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370524.1. 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
	TMIE	NM_001370524.1		c.-66-4757C>A		intron	N/A	NP_001357453.1	A0A2R8YDZ8
	TMIE	NM_001370525.1		c.-66-4757C>A		intron	N/A	NP_001357454.1	A0A2R8YDZ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMIE	ENST00000644830.1		c.-66-4757C>A		intron	N/A	ENSP00000495111.1	A0A2R8YDZ8

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 14148 AN: 147838 Hom.: 778 Cov.: 30

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00442

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0518

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.0697

Gnomad OTH AF: 0.0967

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

GnomAD4 genome AF: 0.0959 AC: 14192 AN: 147950 Hom.: 783 Cov.: 30 AF XY: 0.0957 AC XY: 6911 AN XY: 72234

African (AFR) AF: 0.153 AC: 5937 AN: 38900

American (AMR) AF: 0.0893 AC: 1339 AN: 14990

Ashkenazi Jewish (ASJ) AF: 0.0882 AC: 303 AN: 3436

East Asian (EAS) AF: 0.129 AC: 660 AN: 5100

South Asian (SAS) AF: 0.104 AC: 489 AN: 4712

European-Finnish (FIN) AF: 0.0518 AC: 537 AN: 10370

Middle Eastern (MID) AF: 0.127 AC: 36 AN: 284

European-Non Finnish (NFE) AF: 0.0698 AC: 4690 AN: 67206

Other (OTH) AF: 0.0963 AC: 197 AN: 2046

Alfa AF: 0.0293 Hom.: 14

Bravo AF: 0.0982

Asia WGS AF: 0.130 AC: 453 AN: 3472

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	-0.74
CADD	Benign	6.4
DANN	Benign	0.79
PhyloP100		0.44
PromoterAI		-0.0093	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs77829267; hg19: chr3-46742523;