rs3743601

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001077418.3(TMEM231):​c.16C>T​(p.Leu6Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000015 in 1,332,992 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

TMEM231
NM_001077418.3 missense

Scores

1
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.96
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM231NM_001077418.3 linkuse as main transcriptc.16C>T p.Leu6Phe missense_variant 1/7 ENST00000258173.11 NP_001070886.1
TMEM231NM_001077416.2 linkuse as main transcriptc.78C>T p.Ser26= synonymous_variant 1/6 NP_001070884.2
TMEM231NR_074083.2 linkuse as main transcriptn.59C>T non_coding_transcript_exon_variant 1/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM231ENST00000258173.11 linkuse as main transcriptc.16C>T p.Leu6Phe missense_variant 1/71 NM_001077418.3 ENSP00000258173 P1Q9H6L2-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000150
AC:
2
AN:
1332992
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
651880
show subpopulations
Gnomad4 AFR exome
AF:
0.0000351
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:
9.48e-7
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
AlphaMissense
Benign
0.31
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T;T
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Benign
0.47
N
LIST_S2
Uncertain
0.90
D;D
M_CAP
Uncertain
0.094
D
MetaRNN
Uncertain
0.52
D;D
MetaSVM
Benign
-0.44
T
MutationTaster
Benign
0.15
P;P;P
PROVEAN
Benign
-1.9
N;N
REVEL
Uncertain
0.36
Sift
Benign
0.18
T;T
Sift4G
Uncertain
0.030
D;D
Polyphen
0.51
P;.
Vest4
0.38
MutPred
0.70
Loss of stability (P = 0.0341);Loss of stability (P = 0.0341);
MVP
0.42
ClinPred
0.84
D
GERP RS
4.6
Varity_R
0.21
gMVP
0.57

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: rs3743601; hg19: chr16-75590092; API