3-46701259-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001370524.1(TMIE):c.-66-4531A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 361,318 control chromosomes in the GnomAD database, including 12,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3913 hom., cov: 31)
  • Exomes 𝑓: 0.30 (8935 hom.)
• Consequence: TMIE NM_001370524.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.38

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-46701259-A-T is Benign according to our data. Variant chr3-46701259-A-T is described in ClinVar as [Benign]. Clinvar id is 1272920.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMIE	NM_001370524.1	c.-66-4531A>T		intron_variant
TMIE	NM_001370525.1	c.-66-4531A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMIE	ENST00000644830.1	c.-66-4531A>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32138 AN: 150788 Hom.: 3908 Cov.: 31

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.302 AC: 63491 AN: 210426 Hom.: 8935 AF XY: 0.301 AC XY: 33666 AN XY: 111900

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.327

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.213 AC: 32146 AN: 150892 Hom.: 3913 Cov.: 31 AF XY: 0.214 AC XY: 15756 AN XY: 73784

Gnomad4 AFR AF: 0.0876

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.222

Alfa AF: 0.116 Hom.: 191

Bravo AF: 0.205

Asia WGS AF: 0.218 AC: 750 AN: 3452

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

Nov 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.2
Dann	Benign	0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7430680; hg19: chr3-46742749; COSMIC: COSV58405354; COSMIC: COSV58405354;