rs2242407

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001077418.3(TMEM231):c.*8A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,599,648 control chromosomes in the GnomAD database, including 52,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4830 hom., cov: 32)

Exomes 𝑓: 0.25 ( 47357 hom. )

Consequence

TMEM231
NM_001077418.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.467

Publications

16 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
Meckel syndrome, type 11
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
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:

ENSG00000260092 (HGNC:):

ENSG00000260092 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001077418.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.96).

BP6

Variant 16-75539986-T-C is Benign according to our data. Variant chr16-75539986-T-C is described in ClinVar as Benign. ClinVar VariationId is 257328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077418.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMEM231	NM_001077418.3	MANE Select	c.*8A>G	3_prime_UTR	Exon 7 of 7	NP_001070886.1	Q9H6L2-1
TMEM231	NM_001077416.2		c.*8A>G	3_prime_UTR	Exon 6 of 6	NP_001070884.2	Q9H6L2
TMEM231	NR_074083.2		n.1125A>G	non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMEM231	ENST00000258173.11	TSL:1 MANE Select	c.*8A>G	3_prime_UTR	Exon 7 of 7	ENSP00000258173.5	Q9H6L2-1
TMEM231	ENST00000568377.5	TSL:1	c.*8A>G	3_prime_UTR	Exon 6 of 6	ENSP00000476267.1	Q9H6L2-2
TMEM231	ENST00000565067.5	TSL:5	c.*8A>G	3_prime_UTR	Exon 6 of 6	ENSP00000457254.1	H3BTN6

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

37791

AN:

149860

Hom.:

4826

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.230

GnomAD2 exomes

AF:

0.234

AC:

56179

AN:

240376

AF XY:

0.237

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.241

GnomAD4 exome

AF:

0.252

AC:

365984

AN:

1449680

Hom.:

47357

Cov.:

AF XY:

0.252

AC XY:

181851

AN XY:

720562

show subpopulations

African (AFR)

AF:

0.246

AC:

8164

AN:

33234

American (AMR)

AF:

0.127

AC:

5565

AN:

43870

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

4493

AN:

25580

East Asian (EAS)

AF:

0.215

AC:

8522

AN:

39610

South Asian (SAS)

AF:

0.229

AC:

19408

AN:

84620

European-Finnish (FIN)

AF:

0.309

AC:

16338

AN:

52938

Middle Eastern (MID)

AF:

0.226

AC:

1071

AN:

4738

European-Non Finnish (NFE)

AF:

0.260

AC:

287708

AN:

1105222

Other (OTH)

AF:

0.246

AC:

14715

AN:

59868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

12108

24216

36325

48433

60541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9542

19084

28626

38168

47710

<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:

0.252

AC:

37817

AN:

149968

Hom.:

4830

Cov.:

AF XY:

0.251

AC XY:

18380

AN XY:

73354

show subpopulations

African (AFR)

AF:

0.255

AC:

10088

AN:

39558

American (AMR)

AF:

0.182

AC:

2758

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

605

AN:

3470

East Asian (EAS)

AF:

0.227

AC:

1174

AN:

5164

South Asian (SAS)

AF:

0.224

AC:

1077

AN:

4808

European-Finnish (FIN)

AF:

0.308

AC:

3255

AN:

10558

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.264

AC:

17961

AN:

67922

Other (OTH)

AF:

0.233

AC:

487

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1380

2760

4141

5521

6901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.252

Hom.:

2912

Asia WGS

AF:

0.284

AC:

983

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.068

(source)

DANN

Benign

0.33

PhyloP100

-0.47

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over