17-34581127-A-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001304438.2(TMEM132E):c.51A>T(p.Ser17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 1,525,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: TMEM132E NM_001304438.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.543

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 17-34581127-A-T is Benign according to our data. Variant chr17-34581127-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1898823.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-34581127-A-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.543 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132E	NM_001304438.2	c.51A>T	p.Ser17=	synonymous_variant	1/9	ENST00000631683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132E	ENST00000631683.2	c.51A>T	p.Ser17=	synonymous_variant	1/9	5	NM_001304438.2	P1
TMEM132E	ENST00000321639.7	c.51A>T	p.Ser17=	synonymous_variant	1/10	5

Frequencies

GnomAD3 genomes AF: 0.000185 AC: 28 AN: 151688 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000193 AC: 24 AN: 124360 Hom.: 0 AF XY: 0.000233 AC XY: 16 AN XY: 68716

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000916

Gnomad ASJ exome AF: 0.000780

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000129

Gnomad NFE exome AF: 0.000297

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000350 AC: 481 AN: 1373522 Hom.: 0 Cov.: 34 AF XY: 0.000341 AC XY: 231 AN XY: 678306

Gnomad4 AFR exome AF: 0.0000680

Gnomad4 AMR exome AF: 0.0000884

Gnomad4 ASJ exome AF: 0.000326

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000262

Gnomad4 NFE exome AF: 0.000427

Gnomad4 OTH exome AF: 0.000157

GnomAD4 genome AF: 0.000185 AC: 28 AN: 151688 Hom.: 0 Cov.: 34 AF XY: 0.000108 AC XY: 8 AN XY: 74078

Gnomad4 AFR AF: 0.0000726

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000336 Hom.: 0

Bravo AF: 0.000238

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 21, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	3.3
Dann	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs769358704; hg19: chr17-32908146;