Variant chr16-75540132-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001077418.3(TMEM231):c.813G>A(p.Val271=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 1,613,238 control chromosomes in the GnomAD database, including 23,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.099 ( 2475 hom., cov: 33)

Exomes 𝑓: 0.097 ( 21116 hom. )

Consequence

TMEM231
NM_001077418.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.923

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 16-75540132-C-T is Benign according to our data. Variant chr16-75540132-C-T is described in ClinVar as [Benign]. Clinvar id is 130591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.923 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM231	NM_001077418.3 linkuse as main transcript	c.813G>A	p.Val271=	synonymous_variant	7/7	ENST00000258173.11	NP_001070886.1
TMEM231	NM_001077416.2 linkuse as main transcript	c.972G>A	p.Val324=	synonymous_variant	6/6		NP_001070884.2
TMEM231	NR_074083.2 linkuse as main transcript	n.979G>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM231	ENST00000258173.11 linkuse as main transcript	c.813G>A	p.Val271=	synonymous_variant	7/7	1	NM_001077418.3	ENSP00000258173	P1	Q9H6L2-1

Frequencies

GnomAD3 genomes

AF:

0.0995

AC:

15129

AN:

152106

Hom.:

2468

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.108

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.719

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.0674

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0500

Gnomad OTH

AF:

0.109

GnomAD3 exomes

AF:

0.184

AC:

45706

AN:

247938

Hom.:

10066

AF XY:

0.177

AC XY:

23870

AN XY:

134654

show subpopulations

Gnomad AFR exome

AF:

0.0189

Gnomad AMR exome

AF:

0.422

Gnomad ASJ exome

AF:

0.0868

Gnomad EAS exome

AF:

0.754

Gnomad SAS exome

AF:

0.277

Gnomad FIN exome

AF:

0.0670

Gnomad NFE exome

AF:

0.0524

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.0969

AC:

141614

AN:

1461012

Hom.:

21116

Cov.:

AF XY:

0.101

AC XY:

73122

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.0141

Gnomad4 AMR exome

AF:

0.406

Gnomad4 ASJ exome

AF:

0.0862

Gnomad4 EAS exome

AF:

0.742

Gnomad4 SAS exome

AF:

0.272

Gnomad4 FIN exome

AF:

0.0661

Gnomad4 NFE exome

AF:

0.0511

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.0995

AC:

15143

AN:

152226

Hom.:

2475

Cov.:

AF XY:

0.112

AC XY:

8331

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0192

Gnomad4 AMR

AF:

0.284

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.720

Gnomad4 SAS

AF:

0.307

Gnomad4 FIN

AF:

0.0674

Gnomad4 NFE

AF:

0.0500

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.0560

Hom.:

264

Bravo

AF:

0.116

Asia WGS

AF:

0.446

AC:

1546

AN:

3478

EpiCase

AF:

0.0541

EpiControl

AF:

0.0552

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 02, 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	Eurofins Ntd Llc (ga)	May 28, 2015	- -

Joubert syndrome 20;C3809352:Meckel syndrome, type 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

2.4

DANN

Benign

0.82

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