rs547995253

Variant names:

• chr17-34626120-T-C
• rs547995253
• NM_001304438.2:c.68-7T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001304438.2(TMEM132E):​c.68-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM132E NM_001304438.2 splice_region, intron
• Scores: Splicing: ADA: 0.001782
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.686
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-34626120-T-C is Benign according to our data. Variant chr17-34626120-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2873737.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.68-7T>C		splice_region 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.68-7T>C		splice_region intron	N/A	ENSP00000487800.2	Q6IEE7
	TMEM132E	ENST00000321639.7	TSL:5	c.68-7T>C		splice_region intron	N/A	ENSP00000316532.5	A0A494BWY4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1353242 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 663592

African (AFR) AF: 0.00 AC: 0 AN: 30304

American (AMR) AF: 0.00 AC: 0 AN: 28492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20586

East Asian (EAS) AF: 0.00 AC: 0 AN: 36718

South Asian (SAS) AF: 0.00 AC: 0 AN: 68502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3796

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063546

Other (OTH) AF: 0.00 AC: 0 AN: 55794

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0018
dbscSNV1_RF	Benign	0.15
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs547995253; hg19: chr17-32953139;