dbSNP rs2242406: TMEM231:p.Val271Val (chr16-75540132-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001077418.3(TMEM231):c.813G>A(p.Val271Val) 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

Publications

15 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), G2P, PanelApp Australia
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

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM231	NM_001077418.3	MANE Select	c.813G>A	p.Val271Val	synonymous	Exon 7 of 7	NP_001070886.1	Q9H6L2-1
TMEM231	NM_001077416.2		c.972G>A	p.Val324Val	synonymous	Exon 6 of 6	NP_001070884.2	Q9H6L2
TMEM231	NR_074083.2		n.979G>A		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM231	ENST00000258173.11	TSL:1 MANE Select	c.813G>A	p.Val271Val	synonymous	Exon 7 of 7	ENSP00000258173.5	Q9H6L2-1
TMEM231	ENST00000568377.5	TSL:1	c.900G>A	p.Val300Val	synonymous	Exon 6 of 6	ENSP00000476267.1	Q9H6L2-2
TMEM231	ENST00000565067.5	TSL:5	c.669G>A	p.Val223Val	synonymous	Exon 6 of 6	ENSP00000457254.1	H3BTN6

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

GnomAD2 exomes

AF:

0.184

AC:

45706

AN:

247938

AF XY:

0.177

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 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

African (AFR)

AF:

0.0141

AC:

473

AN:

33476

American (AMR)

AF:

0.406

AC:

18102

AN:

44550

Ashkenazi Jewish (ASJ)

AF:

0.0862

AC:

2253

AN:

26122

East Asian (EAS)

AF:

0.742

AC:

29430

AN:

39668

South Asian (SAS)

AF:

0.272

AC:

23455

AN:

86130

European-Finnish (FIN)

AF:

0.0661

AC:

3525

AN:

53352

Middle Eastern (MID)

AF:

0.0876

AC:

505

AN:

5764

European-Non Finnish (NFE)

AF:

0.0511

AC:

56817

AN:

1111610

Other (OTH)

AF:

0.117

AC:

7054

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

4957

9914

14872

19829

24786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2706

5412

8118

10824

13530

<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:

0.0995

AC:

15143

AN:

152226

Hom.:

2475

Cov.:

AF XY:

0.112

AC XY:

8331

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0192

AC:

798

AN:

41568

American (AMR)

AF:

0.284

AC:

4338

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

351

AN:

3472

East Asian (EAS)

AF:

0.720

AC:

3710

AN:

5156

South Asian (SAS)

AF:

0.307

AC:

1478

AN:

4816

European-Finnish (FIN)

AF:

0.0674

AC:

715

AN:

10614

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0500

AC:

3404

AN:

68020

Other (OTH)

AF:

0.110

AC:

233

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

516

1032

1547

2063

2579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.0591

Hom.:

388

Bravo

AF:

0.116

Asia WGS

AF:

0.446

AC:

1546

AN:

3478

EpiCase

AF:

0.0541

EpiControl

AF:

0.0552

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Joubert syndrome 20;C3809352:Meckel syndrome, type 11 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

2.4

(source)

DANN

Benign

0.82

PhyloP100

0.92

Mutation Taster

=91/9

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

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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