3-46701031-GC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001370524.1(TMIE):c.-66-4749del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00885 in 146,250 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0089 (19 hom., cov: 30)
• Consequence: TMIE NM_001370524.1 intron
• Clinical Significance: Likely 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-GC-G is Benign according to our data. Variant chr3-46701031-GC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1189555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00885 (1295/146250) while in subpopulation AFR AF= 0.0276 (1096/39702). AF 95% confidence interval is 0.0262. There are 19 homozygotes in gnomad4. There are 615 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00882 AC: 1289 AN: 146156 Hom.: 19 Cov.: 30

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00352

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00159

Gnomad SAS AF: 0.00153

Gnomad FIN AF: 0.000305

Gnomad MID AF: 0.0161

Gnomad NFE AF: 0.00164

Gnomad OTH AF: 0.00905

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

GnomAD4 genome AF: 0.00885 AC: 1295 AN: 146250 Hom.: 19 Cov.: 30 AF XY: 0.00865 AC XY: 615 AN XY: 71102

Gnomad4 AFR AF: 0.0276

Gnomad4 AMR AF: 0.00351

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00140

Gnomad4 SAS AF: 0.00153

Gnomad4 FIN AF: 0.000305

Gnomad4 NFE AF: 0.00164

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.000783 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 06, 2019

- -

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;