17-34581198-G-A

Variant names:

• chr17-34581198-G-A
• rs7212426
• NM_001304438.2:c.67+55G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001304438.2(TMEM132E):​c.67+55G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,442,410 control chromosomes in the GnomAD database, including 68,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5637 hom., cov: 31)
  • Exomes 𝑓: 0.30 (62436 hom.)
• Consequence: TMEM132E NM_001304438.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.913
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 17-34581198-G-A is Benign according to our data. Variant chr17-34581198-G-A is described in ClinVar as Benign. ClinVar VariationId is 1270337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 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+55G>A		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+55G>A		intron	N/A	ENSP00000487800.2	Q6IEE7
	TMEM132E	ENST00000321639.7	TSL:5	c.67+55G>A		intron	N/A	ENSP00000316532.5	A0A494BWY4

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39114 AN: 151762 Hom.: 5632 Cov.: 31

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.305 AC: 392976 AN: 1290532 Hom.: 62436 AF XY: 0.300 AC XY: 190821 AN XY: 635372

African (AFR) AF: 0.133 AC: 3528 AN: 26446

American (AMR) AF: 0.181 AC: 4838 AN: 26676

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 6406 AN: 21892

East Asian (EAS) AF: 0.287 AC: 8533 AN: 29732

South Asian (SAS) AF: 0.139 AC: 9609 AN: 69244

European-Finnish (FIN) AF: 0.362 AC: 11987 AN: 33120

Middle Eastern (MID) AF: 0.239 AC: 1236 AN: 5174

European-Non Finnish (NFE) AF: 0.323 AC: 331345 AN: 1024304

Other (OTH) AF: 0.287 AC: 15494 AN: 53944

GnomAD4 genome AF: 0.258 AC: 39125 AN: 151878 Hom.: 5637 Cov.: 31 AF XY: 0.258 AC XY: 19172 AN XY: 74200

African (AFR) AF: 0.138 AC: 5742 AN: 41496

American (AMR) AF: 0.238 AC: 3636 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 979 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1283 AN: 5070

South Asian (SAS) AF: 0.125 AC: 600 AN: 4806

European-Finnish (FIN) AF: 0.374 AC: 3952 AN: 10566

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21890 AN: 67878

Other (OTH) AF: 0.282 AC: 594 AN: 2104

Alfa AF: 0.297 Hom.: 1061

Bravo AF: 0.245

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	21
DANN	Benign	0.77
PhyloP100		0.91
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: rs7212426; hg19: chr17-32908217; COSMIC: COSV58697882; COSMIC: COSV58697882;