Variant 2-201628160-TAAA-TA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001044385.3(TMEM237):c.870-13_870-12del variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0501 in 1,585,366 control chromosomes in the GnomAD database, including 2,367 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 485 hom., cov: 31)

Exomes 𝑓: 0.048 ( 1882 hom. )

Consequence

TMEM237
NM_001044385.3 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.95

Variant links:

Genes affected

TMEM237 (HGNC:14432): (transmembrane protein 237) The protein encoded by this gene is a tetraspanin protein that is thought to be involved in WNT signaling. Defects in this gene are a cause of Joubert syndrome-14. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

TMEM237 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-201628160-TAA-T is Benign according to our data. Variant chr2-201628160-TAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 257324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-201628160-TAA-T is described in Lovd as [Likely_benign]. Variant chr2-201628160-TAA-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM237	NM_001044385.3 linkuse as main transcript	c.870-13_870-12del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000409883.7	NP_001037850.1
TMEM237	NM_152388.4 linkuse as main transcript	c.846-13_846-12del		splice_polypyrimidine_tract_variant, intron_variant			NP_689601.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM237	ENST00000409883.7 linkuse as main transcript	c.870-13_870-12del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001044385.3	ENSP00000386264	P4	Q96Q45-1

Frequencies

GnomAD3 genomes

AF:

0.0671

AC:

10204

AN:

152114

Hom.:

484

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.0286

Gnomad AMR

AF:

0.0535

Gnomad ASJ

AF:

0.0499

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0545

Gnomad OTH

AF:

0.0626

GnomAD3 exomes

AF:

0.0428

AC:

9116

AN:

212796

Hom.:

279

AF XY:

0.0424

AC XY:

4858

AN XY:

114564

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.0324

Gnomad ASJ exome

AF:

0.0508

Gnomad EAS exome

AF:

0.000188

Gnomad SAS exome

AF:

0.0165

Gnomad FIN exome

AF:

0.0173

Gnomad NFE exome

AF:

0.0539

Gnomad OTH exome

AF:

0.0444

GnomAD4 exome

AF:

0.0483

AC:

69239

AN:

1433136

Hom.:

1882

AF XY:

0.0474

AC XY:

33704

AN XY:

711262

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.0339

Gnomad4 ASJ exome

AF:

0.0496

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.0175

Gnomad4 FIN exome

AF:

0.0173

Gnomad4 NFE exome

AF:

0.0521

Gnomad4 OTH exome

AF:

0.0480

GnomAD4 genome

AF:

0.0671

AC:

10211

AN:

152230

Hom.:

485

Cov.:

AF XY:

0.0648

AC XY:

4820

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.0534

Gnomad4 ASJ

AF:

0.0499

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.0158

Gnomad4 FIN

AF:

0.0137

Gnomad4 NFE

AF:

0.0544

Gnomad4 OTH

AF:

0.0620

Alfa

AF:

0.0596

Hom.:

Bravo

AF:

0.0730

Asia WGS

AF:

0.0180

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Jan 13, 2016	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 30, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Joubert syndrome 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Familial aplasia of the vermis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.20

Position offset: -11

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over