rs759314500

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001077418.3(TMEM231):​c.915G>T​(p.Thr305Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,206 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. Synonymous variant affecting the same amino acid position (i.e. T305T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMEM231
NM_001077418.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.216
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 Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP7
Synonymous conserved (PhyloP=-0.216 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM231NM_001077418.3 linkc.915G>T p.Thr305Thr synonymous_variant Exon 7 of 7 ENST00000258173.11 NP_001070886.1 Q9H6L2-1
TMEM231NM_001077416.2 linkc.1074G>T p.Thr358Thr synonymous_variant Exon 6 of 6 NP_001070884.2 Q9H6L2
TMEM231NR_074083.2 linkn.1081G>T non_coding_transcript_exon_variant Exon 7 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM231ENST00000258173.11 linkc.915G>T p.Thr305Thr synonymous_variant Exon 7 of 7 1 NM_001077418.3 ENSP00000258173.5 Q9H6L2-1
TMEM231ENST00000568377.5 linkc.1002G>T p.Thr334Thr synonymous_variant Exon 6 of 6 1 ENSP00000476267.1 Q9H6L2-2
TMEM231ENST00000565067.5 linkc.771G>T p.Thr257Thr synonymous_variant Exon 6 of 6 5 ENSP00000457254.1 H3BTN6
TMEM231ENST00000562410.5 linkn.*717G>T non_coding_transcript_exon_variant Exon 7 of 7 1 ENSP00000454582.1 H3BMW7
TMEM231ENST00000570006.5 linkn.*295G>T non_coding_transcript_exon_variant Exon 7 of 7 5 ENSP00000455520.1 H3BPY4
TMEM231ENST00000562410.5 linkn.*717G>T 3_prime_UTR_variant Exon 7 of 7 1 ENSP00000454582.1 H3BMW7
TMEM231ENST00000570006.5 linkn.*295G>T 3_prime_UTR_variant Exon 7 of 7 5 ENSP00000455520.1 H3BPY4
ENSG00000260092ENST00000460606.1 linkn.157+2572G>T intron_variant Intron 2 of 4 1 ENSP00000457544.1 H3BUA1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152182
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461024
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726804
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152182
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
0.37
DANN
Benign
0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs759314500; hg19: chr16-75573928; API