chr16-75545335-A-T

Variant names:

Variant summary

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

The NM_001077418.3(TMEM231):c.582+17T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,603,564 control chromosomes in the GnomAD database, including 52,565 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5240 hom., cov: 27)

Exomes 𝑓: 0.25 ( 47325 hom. )

Consequence

TMEM231
NM_001077418.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.851

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:

ENSG00000260092 (HGNC:):

ENSG00000260092 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=-0.87).

BP6

Variant 16-75545335-A-T is Benign according to our data. Variant chr16-75545335-A-T is described in ClinVar as [Benign]. Clinvar id is 257331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-75545335-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TMEM231	NM_001077418.3 link	c.582+17T>A	intron_variant	Intron 4 of 6	ENST00000258173.11	NP_001070886.1	Q9H6L2-1
TMEM231	NM_001077416.2 link	c.741+17T>A	intron_variant	Intron 3 of 5		NP_001070884.2	Q9H6L2
TMEM231	NR_074083.2 link	n.748+17T>A	intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM231	ENST00000258173.11 link	c.582+17T>A	intron_variant	Intron 4 of 6	1	NM_001077418.3	ENSP00000258173.5	Q9H6L2-1
TMEM231	ENST00000568377.5 link	c.669+17T>A	intron_variant	Intron 3 of 5	1		ENSP00000476267.1	Q9H6L2-2
TMEM231	ENST00000565067.5 link	c.438+491T>A	intron_variant	Intron 3 of 5	5		ENSP00000457254.1	H3BTN6
ENSG00000260092	ENST00000460606.1 link	n.75+17T>A	intron_variant	Intron 1 of 4	1		ENSP00000457544.1	H3BUA1
TMEM231	ENST00000562410.5 link	n.*384+17T>A	intron_variant	Intron 4 of 6	1		ENSP00000454582.1	H3BMW7
TMEM231	ENST00000570006.5 link	n.544+17T>A	intron_variant	Intron 4 of 6	5		ENSP00000455520.1	H3BPY4

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39381

AN:

151826

Hom.:

5234

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.229

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.234

GnomAD3 exomes

AF:

0.239

AC:

58635

AN:

245504

Hom.:

7560

AF XY:

0.242

AC XY:

32233

AN XY:

133256

show subpopulations

Gnomad AFR exome

AF:

0.289

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.267

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.252

AC:

366354

AN:

1451620

Hom.:

47325

Cov.:

AF XY:

0.252

AC XY:

181783

AN XY:

720712

show subpopulations

Gnomad4 AFR exome

AF:

0.286

Gnomad4 AMR exome

AF:

0.131

Gnomad4 ASJ exome

AF:

0.174

Gnomad4 EAS exome

AF:

0.215

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.311

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.259

AC:

39410

AN:

151944

Hom.:

5240

Cov.:

AF XY:

0.257

AC XY:

19111

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.283

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.228

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.309

Gnomad4 NFE

AF:

0.262

Gnomad4 OTH

AF:

0.236

Alfa

AF:

0.178

Hom.:

540

Bravo

AF:

0.249

Asia WGS

AF:

0.286

AC:

992

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 22, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joubert syndrome 20

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 28, 2017

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joubert syndrome 20;C3809352:Meckel syndrome, type 11

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.031

DANN

Benign

0.36

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