Variant rs3743602 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001077418.3(TMEM231):c.-6G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,416,130 control chromosomes in the GnomAD database, including 40,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3813 hom., cov: 33)

Exomes 𝑓: 0.24 ( 36334 hom. )

Consequence

TMEM231
NM_001077418.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.182

Variant links:

Genes affected

TMEM231 (HGNC:37234): (transmembrane protein 231) This gene encodes a transmembrane protein, which is a component of the B9 complex involved in the formation of the diffusion barrier between the cilia and plasma membrane. Mutations in this gene cause Joubert syndrome (JBTS). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

TMEM231 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=-0.71).

BP6

Variant 16-75556215-C-G is Benign according to our data. Variant chr16-75556215-C-G is described in ClinVar as [Benign]. Clinvar id is 257330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-75556215-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TMEM231	NM_001077418.3 linkuse as main transcript	c.-6G>C		5_prime_UTR_variant	1/7	ENST00000258173.11
TMEM231	NM_001077416.2 linkuse as main transcript	c.57G>C	p.Arg19=	synonymous_variant	1/6
TMEM231	NR_074083.2 linkuse as main transcript	n.38G>C		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM231	ENST00000258173.11 linkuse as main transcript	c.-6G>C		5_prime_UTR_variant	1/7	1	NM_001077418.3	P1	Q9H6L2-1

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33136

AN:

152088

Hom.:

3808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.198

GnomAD3 exomes

AF:

0.218

AC:

11887

AN:

54578

Hom.:

1283

AF XY:

0.221

AC XY:

6783

AN XY:

30658

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.241

Gnomad SAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.280

Gnomad NFE exome

AF:

0.244

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.237

AC:

299906

AN:

1263924

Hom.:

36334

Cov.:

AF XY:

0.235

AC XY:

144285

AN XY:

613532

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.244

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.246

Gnomad4 OTH exome

AF:

0.222

GnomAD4 genome

AF:

0.218

AC:

33150

AN:

152206

Hom.:

3813

Cov.:

AF XY:

0.217

AC XY:

16129

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.253

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.302

Gnomad4 NFE

AF:

0.251

Gnomad4 OTH

AF:

0.199

Alfa

AF:

0.239

Hom.:

563

Bravo

AF:

0.204

Asia WGS

AF:

0.238

AC:

825

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 22, 2016	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	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Joubert syndrome 20;C3809352:Meckel syndrome, type 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.3

DANN

Benign

0.86

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