16-75545344-G-C

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+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 1,608,734 control chromosomes in the GnomAD database, including 1,400 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 85 hom., cov: 23)

Exomes 𝑓: 0.038 ( 1315 hom. )

Consequence

TMEM231
NM_001077418.3 splice_region, intron

Scores

Splicing: ADA: 0.00005890

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.17

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=-0.84).

BP6

Variant 16-75545344-G-C is Benign according to our data. Variant chr16-75545344-G-C is described in ClinVar as [Benign]. Clinvar id is 130590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-75545344-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TMEM231	NM_001077418.3 link	c.582+8C>G	splice_region_variant, intron_variant	Intron 4 of 6	ENST00000258173.11	NP_001070886.1	Q9H6L2-1
TMEM231	NM_001077416.2 link	c.741+8C>G	splice_region_variant, intron_variant	Intron 3 of 5		NP_001070884.2	Q9H6L2
TMEM231	NR_074083.2 link	n.748+8C>G	splice_region_variant, intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM231	ENST00000258173.11 link	c.582+8C>G	splice_region_variant, intron_variant	Intron 4 of 6	1	NM_001077418.3	ENSP00000258173.5	Q9H6L2-1
TMEM231	ENST00000568377.5 link	c.669+8C>G	splice_region_variant, intron_variant	Intron 3 of 5	1		ENSP00000476267.1	Q9H6L2-2
TMEM231	ENST00000565067.5 link	c.438+482C>G	intron_variant	Intron 3 of 5	5		ENSP00000457254.1	H3BTN6
ENSG00000260092	ENST00000460606.1 link	n.75+8C>G	splice_region_variant, intron_variant	Intron 1 of 4	1		ENSP00000457544.1	H3BUA1
TMEM231	ENST00000562410.5 link	n.*384+8C>G	splice_region_variant, intron_variant	Intron 4 of 6	1		ENSP00000454582.1	H3BMW7
TMEM231	ENST00000570006.5 link	n.544+8C>G	splice_region_variant, intron_variant	Intron 4 of 6	5		ENSP00000455520.1	H3BPY4

Frequencies

GnomAD3 genomes

AF:

0.0269

AC:

4092

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00647

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0277

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0611

Gnomad FIN

AF:

0.0168

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0388

Gnomad OTH

AF:

0.0364

GnomAD3 exomes

AF:

0.0320

AC:

7924

AN:

247248

Hom.:

215

AF XY:

0.0360

AC XY:

4826

AN XY:

134172

show subpopulations

Gnomad AFR exome

AF:

0.00498

Gnomad AMR exome

AF:

0.0165

Gnomad ASJ exome

AF:

0.0430

Gnomad EAS exome

AF:

0.000894

Gnomad SAS exome

AF:

0.0667

Gnomad FIN exome

AF:

0.0198

Gnomad NFE exome

AF:

0.0371

Gnomad OTH exome

AF:

0.0386

GnomAD4 exome

AF:

0.0385

AC:

56049

AN:

1456538

Hom.:

1315

Cov.:

AF XY:

0.0398

AC XY:

28822

AN XY:

723790

show subpopulations

Gnomad4 AFR exome

AF:

0.00601

Gnomad4 AMR exome

AF:

0.0179

Gnomad4 ASJ exome

AF:

0.0420

Gnomad4 EAS exome

AF:

0.000354

Gnomad4 SAS exome

AF:

0.0685

Gnomad4 FIN exome

AF:

0.0207

Gnomad4 NFE exome

AF:

0.0399

Gnomad4 OTH exome

AF:

0.0398

GnomAD4 genome

AF:

0.0269

AC:

4089

AN:

152196

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

2037

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00645

Gnomad4 AMR

AF:

0.0276

Gnomad4 ASJ

AF:

0.0412

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0614

Gnomad4 FIN

AF:

0.0168

Gnomad4 NFE

AF:

0.0387

Gnomad4 OTH

AF:

0.0360

Alfa

AF:

0.0264

Hom.:

Bravo

AF:

0.0259

EpiCase

AF:

0.0391

EpiControl

AF:

0.0410

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Apr 06, 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. -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

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

-0.84

CADD

Benign

0.096

DANN

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000059

dbscSNV1_RF

Benign

0.0020

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