Variant rs1208081 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.274+23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,556,314 control chromosomes in the GnomAD database, including 321,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 31972 hom., cov: 32)

Exomes 𝑓: 0.64 ( 289313 hom. )

Consequence

TMEM237
NM_001044385.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.499

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 2-201636725-T-C is Benign according to our data. Variant chr2-201636725-T-C is described in ClinVar as [Benign]. Clinvar id is 257317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 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.274+23A>G		intron_variant		ENST00000409883.7	NP_001037850.1
TMEM237	NM_152388.4 linkuse as main transcript	c.250+23A>G		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.274+23A>G		intron_variant		5	NM_001044385.3	ENSP00000386264	P4	Q96Q45-1

Frequencies

GnomAD3 genomes

AF:

0.645

AC:

98076

AN:

152022

Hom.:

31947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.671

Gnomad AMI

AF:

0.742

Gnomad AMR

AF:

0.611

Gnomad ASJ

AF:

0.691

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.591

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.663

Gnomad OTH

AF:

0.648

GnomAD3 exomes

AF:

0.617

AC:

105859

AN:

171686

Hom.:

33233

AF XY:

0.622

AC XY:

56780

AN XY:

91274

show subpopulations

Gnomad AFR exome

AF:

0.671

Gnomad AMR exome

AF:

0.553

Gnomad ASJ exome

AF:

0.707

Gnomad EAS exome

AF:

0.375

Gnomad SAS exome

AF:

0.635

Gnomad FIN exome

AF:

0.600

Gnomad NFE exome

AF:

0.659

Gnomad OTH exome

AF:

0.644

GnomAD4 exome

AF:

0.640

AC:

898068

AN:

1404174

Hom.:

289313

Cov.:

AF XY:

0.640

AC XY:

443849

AN XY:

693516

show subpopulations

Gnomad4 AFR exome

AF:

0.667

Gnomad4 AMR exome

AF:

0.555

Gnomad4 ASJ exome

AF:

0.697

Gnomad4 EAS exome

AF:

0.370

Gnomad4 SAS exome

AF:

0.632

Gnomad4 FIN exome

AF:

0.613

Gnomad4 NFE exome

AF:

0.651

Gnomad4 OTH exome

AF:

0.635

GnomAD4 genome

AF:

0.645

AC:

98153

AN:

152140

Hom.:

31972

Cov.:

AF XY:

0.641

AC XY:

47641

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.670

Gnomad4 AMR

AF:

0.611

Gnomad4 ASJ

AF:

0.691

Gnomad4 EAS

AF:

0.372

Gnomad4 SAS

AF:

0.640

Gnomad4 FIN

AF:

0.591

Gnomad4 NFE

AF:

0.663

Gnomad4 OTH

AF:

0.649

Alfa

AF:

0.655

Hom.:

70311

Bravo

AF:

0.646

Asia WGS

AF:

0.539

AC:

1877

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Joubert syndrome 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.40

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.40

Position offset: 5

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