3-46701033-C-A

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.-66-4757C>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

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=-0.74).
• BP6: Variant 3-46701033-C-A is Benign according to our data. Variant chr3-46701033-C-A is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMIE	NM_001370524.1	c.-66-4757C>A		intron_variant
TMIE	NM_001370525.1	c.-66-4757C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMIE	ENST00000644830.1	c.-66-4757C>A		intron_variant

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

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.0893

Gnomad4 ASJ AF: 0.0882

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0518

Gnomad4 NFE AF: 0.0698

Gnomad4 OTH AF: 0.0963

Alfa AF: 0.0293 Hom.: 14

Bravo AF: 0.0982

Asia WGS AF: 0.130 AC: 453 AN: 3472

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

Dec 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	6.4
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77829267; hg19: chr3-46742523;