chr16-75555936-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077418.3(TMEM231):​c.177G>T​(p.Pro59Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,268 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: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TMEM231
NM_001077418.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0770
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM231NM_001077418.3 linkc.177G>T p.Pro59Pro synonymous_variant Exon 2 of 7 ENST00000258173.11 NP_001070886.1 Q9H6L2-1
TMEM231NM_001077416.2 linkc.336G>T p.Pro112Pro synonymous_variant Exon 1 of 6 NP_001070884.2 Q9H6L2
TMEM231NR_074083.2 linkn.220G>T non_coding_transcript_exon_variant Exon 2 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM231ENST00000258173.11 linkc.177G>T p.Pro59Pro synonymous_variant Exon 2 of 7 1 NM_001077418.3 ENSP00000258173.5 Q9H6L2-1
TMEM231ENST00000568377.5 linkc.264G>T p.Pro88Pro synonymous_variant Exon 1 of 6 1 ENSP00000476267.1 Q9H6L2-2
TMEM231ENST00000565067.5 linkc.177G>T p.Pro59Pro synonymous_variant Exon 2 of 6 5 ENSP00000457254.1 H3BTN6
TMEM231ENST00000562410.5 linkn.177G>T non_coding_transcript_exon_variant Exon 2 of 7 1 ENSP00000454582.1 H3BMW7
TMEM231ENST00000570006.5 linkn.177G>T non_coding_transcript_exon_variant Exon 2 of 7 5 ENSP00000455520.1 H3BPY4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000207
AC:
3
AN:
1452268
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
721638
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000271
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.30
CADD
Benign
13
DANN
Benign
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-75589834; API