16-75556260-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000562410.5(TMEM231):n.-51G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,382,836 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 43 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 27 hom. )

Consequence

TMEM231
ENST00000562410.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.110

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Joubert syndrome 20
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Joubert syndrome with oculorenal defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
orofaciodigital syndrome III
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TMEM231 links:

ENSG00000259992 (HGNC:):

ENSG00000259992 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 16-75556260-C-T is Benign according to our data. Variant chr16-75556260-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 516234.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 = 0.0122 (1862/152332) while in subpopulation AFR AF = 0.0415 (1727/41580). AF 95% confidence interval is 0.0399. There are 43 homozygotes in GnomAd4. There are 853 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TMEM231	NM_001077416.2 link	c.12G>A	p.Arg4Arg	synonymous_variant	Exon 1 of 6		NP_001070884.2
TMEM231	NM_001077418.3 link	c.-51G>A		upstream_gene_variant		ENST00000258173.11	NP_001070886.1
TMEM231	NR_074083.2 link	n.-8G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
TMEM231	ENST00000562410.5 link	n.-51G>A	non_coding_transcript_exon_variant	Exon 1 of 7	1		ENSP00000454582.1
TMEM231	ENST00000562410.5 link	n.-51G>A	5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000454582.1
TMEM231	ENST00000258173.11 link	c.-51G>A	upstream_gene_variant		1	NM_001077418.3	ENSP00000258173.5
TMEM231	ENST00000568377.5 link	c.-61G>A	upstream_gene_variant		1		ENSP00000476267.1
TMEM231	ENST00000565067.5 link	c.-51G>A	upstream_gene_variant		5		ENSP00000457254.1
TMEM231	ENST00000570006.5 link	n.-51G>A	upstream_gene_variant		5		ENSP00000455520.1

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1856

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0415

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00680

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:

0.000132

Gnomad OTH

AF:

0.0100

GnomAD4 exome

AF:

0.00107

AC:

1318

AN:

1230504

Hom.:

Cov.:

AF XY:

0.000946

AC XY:

563

AN XY:

594890

show subpopulations

African (AFR)

AF:

0.0420

AC:

1030

AN:

24498

American (AMR)

AF:

0.00343

AC:

AN:

13716

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

17338

East Asian (EAS)

AF:

0.00

AC:

AN:

29230

South Asian (SAS)

AF:

0.000125

AC:

AN:

56104

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29610

Middle Eastern (MID)

AF:

0.00181

AC:

AN:

4978

European-Non Finnish (NFE)

AF:

0.0000727

AC:

AN:

1004140

Other (OTH)

AF:

0.00295

AC:

150

AN:

50890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

138

206

275

344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0122

AC:

1862

AN:

152332

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

853

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0415

AC:

1727

AN:

41580

American (AMR)

AF:

0.00679

AC:

104

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68034

Other (OTH)

AF:

0.00992

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

164

247

329

411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00627

Hom.:

Bravo

AF:

0.0135

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 06, 2017

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. -

Joubert syndrome 20;C3809352:Meckel syndrome, type 11

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely 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

-0.72

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

-0.11

PromoterAI

0.023

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over