1-1535723-G-T

Variant summary

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

The NM_001114748.2(TMEM240):​c.239C>A​(p.Thr80Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000129 in 1,550,376 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T80M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

TMEM240
NM_001114748.2 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.62
Variant links:
Genes affected
TMEM240 (HGNC:25186): (transmembrane protein 240) This gene encodes a transmembrane-domain containing protein found in the brain and cerebellum. Mutations in this gene result in spinocerebellar ataxia 21. [provided by RefSeq, Dec 2014]

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
TMEM240NM_001114748.2 linkuse as main transcriptc.239C>A p.Thr80Lys missense_variant 3/4 ENST00000378733.9 NP_001108220.1 Q5SV17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM240ENST00000378733.9 linkuse as main transcriptc.239C>A p.Thr80Lys missense_variant 3/42 NM_001114748.2 ENSP00000368007.4 Q5SV17

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
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:
7.15e-7
AC:
1
AN:
1398198
Hom.:
0
Cov.:
33
AF XY:
0.00000145
AC XY:
1
AN XY:
689652
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:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74338
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
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Uncertain
0.014
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
28
DANN
Benign
0.90
DEOGEN2
Uncertain
0.65
D;D
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.44
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.87
.;D
M_CAP
Uncertain
0.27
D
MetaRNN
Uncertain
0.55
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;N
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-3.5
D;D
REVEL
Uncertain
0.43
Sift
Benign
0.064
T;T
Sift4G
Benign
0.12
T;T
Polyphen
0.43
B;B
Vest4
0.79
MutPred
0.30
Gain of ubiquitination at T80 (P = 0.0131);Gain of ubiquitination at T80 (P = 0.0131);
MVP
0.061
ClinPred
0.30
T
GERP RS
2.4
Varity_R
0.27
gMVP
0.81

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

LitVar

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

Other links and lift over

dbSNP: rs606231454; hg19: chr1-1471103; API