rs201537260

Variant summary

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

The NM_015140.4(TTLL12):​c.1756A>T​(p.Met586Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000282 in 1,419,626 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. M586V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TTLL12
NM_015140.4 missense

Scores

11
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.14
Variant links:
Genes affected
TTLL12 (HGNC:28974): (tubulin tyrosine ligase like 12) Enables H4K20me3 modified histone binding activity and tubulin binding activity. Involved in negative regulation of type I interferon-mediated signaling pathway and regulation of mitotic cell cycle. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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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 rank MANE Protein UniProt
TTLL12NM_015140.4 linkc.1756A>T p.Met586Leu missense_variant Exon 13 of 14 ENST00000216129.7 NP_055955.1 Q14166A0A024R4U3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TTLL12ENST00000216129.7 linkc.1756A>T p.Met586Leu missense_variant Exon 13 of 14 1 NM_015140.4 ENSP00000216129.6 Q14166
TTLL12ENST00000494035.1 linkc.19A>T p.Met7Leu missense_variant Exon 3 of 4 2 ENSP00000476297.1 V9GY16
TTLL12ENST00000484711.1 linkn.887A>T non_coding_transcript_exon_variant Exon 2 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000282
AC:
4
AN:
1419626
Hom.:
0
Cov.:
30
AF XY:
0.00000142
AC XY:
1
AN XY:
702386
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:
0.00000367
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
Uncertain
0.41
BayesDel_addAF
Uncertain
0.042
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.066
T;T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.65
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-2.0
N;.
REVEL
Benign
0.25
Sift
Uncertain
0.021
D;.
Sift4G
Benign
0.095
T;T
Polyphen
0.84
P;.
Vest4
0.73
MutPred
0.64
Loss of methylation at K588 (P = 0.0878);.;
MVP
0.19
MPC
0.33
ClinPred
0.91
D
GERP RS
5.5
Varity_R
0.39
gMVP
0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-43564807; API