17-34587940-C-CTT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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 id is 3779448.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132E	NM_001304438.2	c.67+6798_67+6799dupTT		intron_variant	Intron 1 of 8	ENST00000631683.2	NP_001291367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM132E	ENST00000631683.2	c.67+6797_67+6798insTT		intron_variant	Intron 1 of 8	5	NM_001304438.2	ENSP00000487800.2
TMEM132E	ENST00000321639.7	c.67+6797_67+6798insTT		intron_variant	Intron 1 of 9	5		ENSP00000316532.5

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: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial cancer of breast;C2675520:Breast-ovarian cancer, familial, susceptibility to, 2 Pathogenic:1

Apr 01, 2019

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-32914959;