Variant rs77570029 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001044385.3(TMEM237):c.1134T>C(p.Tyr378Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 1,596,412 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00020 ( 3 hom. )

Consequence

TMEM237
NM_001044385.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.313

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:

TMEM237 (HGNC:):

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=-0.81).

BP6

Variant 2-201626051-A-G is Benign according to our data. Variant chr2-201626051-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 257315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00193 (294/152226) while in subpopulation AFR AF= 0.00655 (272/41522). AF 95% confidence interval is 0.00591. There are 1 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM237	NM_001044385.3 linkuse as main transcript	c.1134T>C	p.Tyr378Tyr	synonymous_variant	12/13	ENST00000409883.7	NP_001037850.1	Q96Q45-1
TMEM237	NM_152388.4 linkuse as main transcript	c.1110T>C	p.Tyr370Tyr	synonymous_variant	12/13		NP_689601.2	Q96Q45-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM237	ENST00000409883.7 linkuse as main transcript	c.1134T>C	p.Tyr378Tyr	synonymous_variant	12/13	5	NM_001044385.3	ENSP00000386264.2		Q96Q45-1

Frequencies

GnomAD3 genomes

AF:

0.00190

AC:

289

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00645

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000468

AC:

104

AN:

222278

Hom.:

AF XY:

0.000376

AC XY:

AN XY:

119758

show subpopulations

Gnomad AFR exome

AF:

0.00629

Gnomad AMR exome

AF:

0.000573

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000197

AC:

284

AN:

1444186

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

132

AN XY:

716568

show subpopulations

Gnomad4 AFR exome

AF:

0.00567

Gnomad4 AMR exome

AF:

0.000572

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000453

Gnomad4 OTH exome

AF:

0.00107

GnomAD4 genome

AF:

0.00193

AC:

294

AN:

152226

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00655

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00109

Hom.:

Bravo

AF:

0.00229

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 02, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 30, 2018	- -

Joubert syndrome 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.060

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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