chr3-46709583-TAAGAAGAAGAAGAAG-T

Variant names:

• chr3-46709583-TAAGAAGAAGAAGAAG-T
• rs10578999
• NM_147196.3:c.379_393delAAGAAGAAGAAGAAG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1

The NM_147196.3(TMIE):​c.379_393delAAGAAGAAGAAGAAG​(p.Lys127_Lys131del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMIE NM_147196.3 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54

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 Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a chain Transmembrane inner ear expressed protein (size 128) in uniprot entity TMIE_HUMAN there are 6 pathogenic changes around while only 2 benign (75%) in NM_147196.3

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMIE	NM_147196.3	c.379_393delAAGAAGAAGAAGAAG	p.Lys127_Lys131del	conservative_inframe_deletion	Exon 4 of 4	ENST00000643606.3	NP_671729.2
TMIE	NM_001370524.1	c.220_234delAAGAAGAAGAAGAAG	p.Lys74_Lys78del	conservative_inframe_deletion	Exon 4 of 4		NP_001357453.1
TMIE	NM_001370525.1	c.220_234delAAGAAGAAGAAGAAG	p.Lys74_Lys78del	conservative_inframe_deletion	Exon 5 of 5		NP_001357454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMIE	ENST00000643606.3	c.379_393delAAGAAGAAGAAGAAG	p.Lys127_Lys131del	conservative_inframe_deletion	Exon 4 of 4		NM_147196.3	ENSP00000494576.2
TMIE	ENST00000644830.1	c.220_234delAAGAAGAAGAAGAAG	p.Lys74_Lys78del	conservative_inframe_deletion	Exon 4 of 4			ENSP00000495111.1
TMIE	ENST00000651652.1	c.*301_*315delAAGAAGAAGAAGAAG		3_prime_UTR_variant	Exon 2 of 2			ENSP00000498953.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.13e-7 AC: 1 AN: 1402592 Hom.: 0 AF XY: 0.00000143 AC XY: 1 AN XY: 698904

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.41e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

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: rs10578999; hg19: chr3-46751073;