rs11657603

Variant names:

• chr17-34608994-G-A
• rs11657603
• NM_001304438.2:c.68-17133G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-34608994-G-A
• chr17-34608994-G-C

Variant summary

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

The NM_001304438.2(TMEM132E):​c.68-17133G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 152,004 control chromosomes in the GnomAD database, including 26,008 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 0.58 (26008 hom., cov: 32)
• Consequence: TMEM132E NM_001304438.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652
• Publications: 2 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132E	NM_001304438.2	c.68-17133G>A		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.68-17133G>A		intron_variant	Intron 1 of 8	5	NM_001304438.2	ENSP00000487800.2
TMEM132E	ENST00000321639.7	c.68-17133G>A		intron_variant	Intron 1 of 9	5		ENSP00000316532.5

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87403 AN: 151886 Hom.: 26008 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.575 AC: 87430 AN: 152004 Hom.: 26008 Cov.: 32 AF XY: 0.578 AC XY: 42975 AN XY: 74288

African (AFR) AF: 0.416 AC: 17227 AN: 41438

American (AMR) AF: 0.711 AC: 10866 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2110 AN: 3468

East Asian (EAS) AF: 0.667 AC: 3441 AN: 5162

South Asian (SAS) AF: 0.592 AC: 2855 AN: 4820

European-Finnish (FIN) AF: 0.634 AC: 6683 AN: 10548

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42236 AN: 67978

Other (OTH) AF: 0.593 AC: 1249 AN: 2108

Alfa AF: 0.613 Hom.: 15651

Bravo AF: 0.575

Asia WGS AF: 0.623 AC: 2164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.72
DANN	Benign	0.41
PhyloP100		-0.65
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: rs11657603; hg19: chr17-32936013;