rs367694491

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_015140.4(TTLL12):​c.1774G>C​(p.Gly592Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,407,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G592S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

TTLL12
NM_015140.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.382
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07494813).
BP6
Variant 22-43168783-C-G is Benign according to our data. Variant chr22-43168783-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3184559.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TTLL12NM_015140.4 linkc.1774G>C p.Gly592Arg 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.1774G>C p.Gly592Arg missense_variant Exon 13 of 14 1 NM_015140.4 ENSP00000216129.6 Q14166
TTLL12ENST00000494035.1 linkc.37G>C p.Gly13Arg missense_variant Exon 3 of 4 2 ENSP00000476297.1 V9GY16
TTLL12ENST00000484711.1 linkn.905G>C non_coding_transcript_exon_variant Exon 2 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000599
AC:
1
AN:
166874
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
88622
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000822
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.10e-7
AC:
1
AN:
1407480
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
695270
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:
0.00
Gnomad4 OTH exome
AF:
0.0000171
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000855
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Oct 10, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.063
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
4.3
DANN
Benign
0.63
DEOGEN2
Benign
0.0058
T;T
Eigen
Benign
-0.92
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.072
N
LIST_S2
Benign
0.36
T;T
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.075
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.76
N;.
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.25
N;.
REVEL
Benign
0.027
Sift
Benign
0.70
T;.
Sift4G
Benign
0.61
T;T
Polyphen
0.0020
B;.
Vest4
0.12
MutPred
0.56
Gain of MoRF binding (P = 0.034);.;
MVP
0.34
MPC
0.11
ClinPred
0.017
T
GERP RS
2.1
Varity_R
0.021
gMVP
0.44

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: rs367694491; hg19: chr22-43564789; API