rs397517868

chr3-46709604-GAAGA-GG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_147196.3(TMIE):c.388_391delinsG(p.Lys130_Lys131delinsGlu) variant causes a protein altering change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. K130K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMIE NM_147196.3 protein_altering
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.51

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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 3-46709605-AAGA-G is Benign according to our data. Variant chr3-46709605-AAGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 47961.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMIE	NM_147196.3	c.388_391delinsG	p.Lys130_Lys131delinsGlu	protein_altering_variant	4/4	ENST00000643606.3
TMIE	NM_001370524.1	c.229_232delinsG	p.Lys77_Lys78delinsGlu	protein_altering_variant	4/4
TMIE	NM_001370525.1	c.229_232delinsG	p.Lys77_Lys78delinsGlu	protein_altering_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMIE	ENST00000643606.3	c.388_391delinsG	p.Lys130_Lys131delinsGlu	protein_altering_variant	4/4		NM_147196.3	P1
TMIE	ENST00000644830.1	c.229_232delinsG	p.Lys77_Lys78delinsGlu	protein_altering_variant	4/4
TMIE	ENST00000651652.1	c.*310_*313delinsG		3_prime_UTR_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 30, 2012

Lys130_Lys131delinsGlu in exon 4 of TMIE: This variant represents a missense cha nge, Lys131Glu (dbSNP ID rs201683042), that arose on the background of the very common benign variant Lys131del (dbSNP ID rs10578999). Neither variant, nor the combination of variants, is expected to impact the protein as the 3 bp deletion is extremely common and the missense change occurs in a mammal (rabbit has the L ys131Glu in its normal TMIE protein). -

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: rs397517868; hg19: chr3-46751095;