Variant 2-201629867-C-T 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.554-15G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000394 in 1,605,094 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 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 3 hom. )

Consequence

TMEM237
NM_001044385.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.34

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-201629867-C-T is Benign according to our data. Variant chr2-201629867-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 257320.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 = 0.00195 (297/152140) while in subpopulation AFR AF= 0.00651 (270/41494). AF 95% confidence interval is 0.00587. There are 1 homozygotes in gnomad4. There are 135 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.554-15G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000409883.7	NP_001037850.1
TMEM237	NM_152388.4 linkuse as main transcript	c.530-15G>A		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.554-15G>A		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001044385.3	ENSP00000386264	P4	Q96Q45-1

Frequencies

GnomAD3 genomes

AF:

0.00192

AC:

292

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00641

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

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:

0.0000441

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000559

AC:

133

AN:

237740

Hom.:

AF XY:

0.000466

AC XY:

AN XY:

128690

show subpopulations

Gnomad AFR exome

AF:

0.00592

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000580

Gnomad SAS exome

AF:

0.0000746

Gnomad FIN exome

AF:

0.0000469

Gnomad NFE exome

AF:

0.0000546

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.000231

AC:

335

AN:

1452954

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

155

AN XY:

722120

show subpopulations

Gnomad4 AFR exome

AF:

0.00548

Gnomad4 AMR exome

AF:

0.000943

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000721

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.00112

GnomAD4 genome

AF:

0.00195

AC:

297

AN:

152140

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

135

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00651

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000897

Hom.:

Bravo

AF:

0.00233

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.83

CADD

Benign

3.7

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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