17-34584149-C-T

Variant names:

• chr17-34584149-C-T
• rs4795942
• NM_001304438.2:c.67+3006C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304438.2(TMEM132E):​c.67+3006C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 152,160 control chromosomes in the GnomAD database, including 38,985 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (38985 hom., cov: 34)
• Consequence: TMEM132E NM_001304438.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

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+3006C>T		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+3006C>T		intron	N/A	ENSP00000487800.2	Q6IEE7
	TMEM132E	ENST00000321639.7	TSL:5	c.67+3006C>T		intron	N/A	ENSP00000316532.5	A0A494BWY4

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108340 AN: 152042 Hom.: 38954 Cov.: 34

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.713 AC: 108426 AN: 152160 Hom.: 38985 Cov.: 34 AF XY: 0.709 AC XY: 52726 AN XY: 74402

African (AFR) AF: 0.666 AC: 27623 AN: 41486

American (AMR) AF: 0.672 AC: 10280 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2333 AN: 3470

East Asian (EAS) AF: 0.609 AC: 3146 AN: 5164

South Asian (SAS) AF: 0.491 AC: 2371 AN: 4826

European-Finnish (FIN) AF: 0.803 AC: 8520 AN: 10612

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51695 AN: 67992

Other (OTH) AF: 0.708 AC: 1496 AN: 2114

Alfa AF: 0.736 Hom.: 32766

Bravo AF: 0.706

Asia WGS AF: 0.508 AC: 1769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.48
PhyloP100		0.024
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4795942; hg19: chr17-32911168;