NM_001304438.2:c.67+6798_67+6799dupTT

Variant names:

• chr17-34587940-C-CTT
• NM_001304438.2:c.67+6798_67+6799dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_001304438.2(TMEM132E):​c.67+6798_67+6799dupTT variant causes a intron 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 Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM132E NM_001304438.2 intron
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.180
• Publications: 0 publications found

Genes affected

TMEM132E (HGNC:26991): (transmembrane protein 132E) Involved in posterior lateral line neuromast hair cell development. Predicted to be located in cell body. Implicated in autosomal recessive nonsyndromic deafness 99. [provided by Alliance of Genome Resources, Apr 2022]

TMEM132E Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive 99

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

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-34587940-C-CTT is Pathogenic according to our data. Variant chr17-34587940-C-CTT is described in ClinVar as Pathogenic. ClinVar VariationId is 3779448.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304438.2. 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
	TMEM132E	NM_001304438.2	MANE Select	c.67+6798_67+6799dupTT		intron	N/A	NP_001291367.1	Q6IEE7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132E	ENST00000631683.2	TSL:5 MANE Select	c.67+6797_67+6798insTT		intron	N/A	ENSP00000487800.2	Q6IEE7
	TMEM132E	ENST00000321639.7	TSL:5	c.67+6797_67+6798insTT		intron	N/A	ENSP00000316532.5	A0A494BWY4

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: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Familial cancer of breast;C2675520:Breast-ovarian cancer, familial, susceptibility to, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18

Splicing

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

Other links and lift over

hg19: chr17-32914959;