rs141817764

Positions:

chr2-201636828-T-C

Variant summary

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

The NM_001044385.3(TMEM237):c.194A>G(p.Asn65Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 1,605,538 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 3 hom. )

Consequence

TMEM237
NM_001044385.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.382

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 (MetaRNN=0.0043639243).

BP6

Variant 2-201636828-T-C is Benign according to our data. Variant chr2-201636828-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 257316.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 (294/152356) while in subpopulation AFR AF= 0.00652 (271/41586). AF 95% confidence interval is 0.00588. There are 1 homozygotes in gnomad4. There are 133 alleles in male gnomad4 subpopulation. Median coverage is 32. 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.194A>G	p.Asn65Ser	missense_variant	5/13	ENST00000409883.7	NP_001037850.1	Q96Q45-1
TMEM237	NM_152388.4 linkuse as main transcript	c.170A>G	p.Asn57Ser	missense_variant	5/13		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.194A>G	p.Asn65Ser	missense_variant	5/13	5	NM_001044385.3	ENSP00000386264.2		Q96Q45-1

Frequencies

GnomAD3 genomes

AF:

0.00190

AC:

289

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00642

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:

0.0000147

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000446

AC:

105

AN:

235590

Hom.:

AF XY:

0.000345

AC XY:

AN XY:

127454

show subpopulations

Gnomad AFR exome

AF:

0.00607

Gnomad AMR exome

AF:

0.000483

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000580

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000939

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.000198

AC:

288

AN:

1453182

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

134

AN XY:

721846

show subpopulations

Gnomad4 AFR exome

AF:

0.00563

Gnomad4 AMR exome

AF:

0.000527

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000632

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00193

AC:

294

AN:

152356

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

133

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00652

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:

0.0000147

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000662

Hom.:

Bravo

AF:

0.00229

ESP6500AA

AF:

0.00570

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000596

AC:

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

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

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 01, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Joubert syndrome 14

Benign:1

Likely 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

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.0

DANN

Benign

0.17

DEOGEN2

Benign

0.00086

.;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.082

T;T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.5

.;N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

0.23

N;N;.

REVEL

Benign

0.059

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Vest4

0.044

MVP

0.081

MPC

0.034

ClinPred

0.0031

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.014

gMVP

0.025

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