rs397517868

Variant names:

• chr3-46709605-AAGA-G
• rs397517868
• NM_147196.3:c.388_391delAAGAinsG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_147196.3(TMIE):​c.388_391delAAGAinsG​(p.Lys130_Lys131delinsGlu) variant causes a missense, conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 missense, conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.51
• Publications: 0 publications found

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]

TMIE Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 6

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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 VariationId is 47961.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147196.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMIE	NM_147196.3	MANE Select	c.388_391delAAGAinsG	p.Lys130_Lys131delinsGlu	missense conservative_inframe_deletion	Exon 4 of 4	NP_671729.2	Q8NEW7
	TMIE	NM_001370524.1		c.229_232delAAGAinsG	p.Lys77_Lys78delinsGlu	missense conservative_inframe_deletion	Exon 4 of 4	NP_001357453.1	A0A2R8YDZ8
	TMIE	NM_001370525.1		c.229_232delAAGAinsG	p.Lys77_Lys78delinsGlu	missense conservative_inframe_deletion	Exon 5 of 5	NP_001357454.1	A0A2R8YDZ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMIE	ENST00000643606.3	MANE Select	c.388_391delAAGAinsG	p.Lys130_Lys131delinsGlu	missense conservative_inframe_deletion	Exon 4 of 4	ENSP00000494576.2	Q8NEW7
	TMIE	ENST00000644830.1		c.229_232delAAGAinsG	p.Lys77_Lys78delinsGlu	missense conservative_inframe_deletion	Exon 4 of 4	ENSP00000495111.1	A0A2R8YDZ8
	TMIE	ENST00000651652.1		c.*310_*313delAAGAinsG		3_prime_UTR	Exon 2 of 2	ENSP00000498953.1	A0A494C1A3

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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs397517868;

hg19: chr3-46751095;