dbSNP rs115739052: TMEM231:n.-51G>C (chr16-75556260-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000562410.5(TMEM231):n.-51G>C 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 0.00000325 in 1,230,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

TMEM231
ENST00000562410.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TMEM231	NM_001077416.2 link	c.12G>C	p.Arg4Ser	missense_variant	Exon 1 of 6		NP_001070884.2
TMEM231	NM_001077418.3 link	c.-51G>C		upstream_gene_variant		ENST00000258173.11	NP_001070886.1
TMEM231	NR_074083.2 link	n.-8G>C		upstream_gene_variant

Ensembl

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000325

AC:

AN:

1230506

Hom.:

Cov.:

AF XY:

0.00000336

AC XY:

AN XY:

594892

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24500

American (AMR)

AF:

0.00

AC:

AN:

13716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17338

East Asian (EAS)

AF:

0.00

AC:

AN:

29230

South Asian (SAS)

AF:

0.00

AC:

AN:

56104

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4978

European-Non Finnish (NFE)

AF:

0.00000398

AC:

AN:

1004140

Other (OTH)

AF:

0.00

AC:

AN:

50890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.7

(source)

DANN

Benign

0.87

PhyloP100

-0.11

PromoterAI

0.016

Neutral

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over