Genetic Variant TMEM237:c.-409C>G (chr2-201642630-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152388.4(TMEM237):c.-4C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 1,608,188 control chromosomes in the GnomAD database, including 3,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.074 ( 876 hom., cov: 32)

Exomes 𝑓: 0.028 ( 2225 hom. )

Consequence

TMEM237
NM_152388.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.139

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-201642630-G-C is Benign according to our data. Variant chr2-201642630-G-C is described in ClinVar as [Benign]. Clinvar id is 137672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM237	NM_001044385.3 link	c.42+729C>G		intron_variant	Intron 1 of 12	ENST00000409883.7	NP_001037850.1	Q96Q45-1
TMEM237	NM_152388.4 link	c.-4C>G		5_prime_UTR_variant	Exon 1 of 13		NP_689601.2	Q96Q45-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM237	ENST00000409883.7 link	c.42+729C>G		intron_variant	Intron 1 of 12	5	NM_001044385.3	ENSP00000386264.2		Q96Q45-1

Frequencies

GnomAD3 genomes

AF:

0.0742

AC:

11297

AN:

152186

Hom.:

873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0302

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.0478

Gnomad FIN

AF:

0.0514

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.0156

Gnomad OTH

AF:

0.0540

GnomAD3 exomes

AF:

0.0473

AC:

11381

AN:

240368

Hom.:

769

AF XY:

0.0445

AC XY:

5857

AN XY:

131478

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.0164

Gnomad ASJ exome

AF:

0.0190

Gnomad EAS exome

AF:

0.232

Gnomad SAS exome

AF:

0.0387

Gnomad FIN exome

AF:

0.0495

Gnomad NFE exome

AF:

0.0173

Gnomad OTH exome

AF:

0.0343

GnomAD4 exome

AF:

0.0284

AC:

41298

AN:

1455884

Hom.:

2225

Cov.:

AF XY:

0.0279

AC XY:

20188

AN XY:

724416

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.0176

Gnomad4 ASJ exome

AF:

0.0206

Gnomad4 EAS exome

AF:

0.256

Gnomad4 SAS exome

AF:

0.0376

Gnomad4 FIN exome

AF:

0.0462

Gnomad4 NFE exome

AF:

0.0143

Gnomad4 OTH exome

AF:

0.0415

GnomAD4 genome

AF:

0.0742

AC:

11306

AN:

152304

Hom.:

876

Cov.:

AF XY:

0.0761

AC XY:

5671

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.184

Gnomad4 AMR

AF:

0.0302

Gnomad4 ASJ

AF:

0.0219

Gnomad4 EAS

AF:

0.224

Gnomad4 SAS

AF:

0.0472

Gnomad4 FIN

AF:

0.0514

Gnomad4 NFE

AF:

0.0156

Gnomad4 OTH

AF:

0.0582

Alfa

AF:

0.0309

Hom.:

Bravo

AF:

0.0772

Asia WGS

AF:

0.133

AC:

461

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 15, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Feb 08, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.1

DANN

Benign

0.57

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

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