chr3-46701031-G-GC

Position:

• chr3-46701031-G-GC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001370524.1(TMIE):​c.-66-4749dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 146,268 control chromosomes in the GnomAD database, including 266 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.038 (266 hom., cov: 30)
• Consequence: TMIE NM_001370524.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.439

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-46701031-G-GC is Benign according to our data. Variant chr3-46701031-G-GC is described in ClinVar as [Benign]. Clinvar id is 1239252.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMIE	NM_001370524.1	c.-66-4749dup		intron_variant
TMIE	NM_001370525.1	c.-66-4749dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMIE	ENST00000644830.1	c.-66-4749dup		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 5580 AN: 146174 Hom.: 271 Cov.: 30

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.000295

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.00720

Gnomad FIN AF: 0.00233

Gnomad MID AF: 0.00645

Gnomad NFE AF: 0.00832

Gnomad OTH AF: 0.0307

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

GnomAD4 genome AF: 0.0381 AC: 5569 AN: 146268 Hom.: 266 Cov.: 30 AF XY: 0.0364 AC XY: 2592 AN XY: 71112

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0242

Gnomad4 ASJ AF: 0.000295

Gnomad4 EAS AF: 0.0138

Gnomad4 SAS AF: 0.00721

Gnomad4 FIN AF: 0.00233

Gnomad4 NFE AF: 0.00833

Gnomad4 OTH AF: 0.0304

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

Aug 21, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34094160; hg19: chr3-46742521;