Variant 1-1179268-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130045.2(TTLL10):c.53C>T(p.Thr18Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000058 in 1,550,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

TTLL10
NM_001130045.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.809

Variant links:

Genes affected

TTLL10 (HGNC:26693): (tubulin tyrosine ligase like 10) Predicted to enable protein-glycine ligase activity, elongating. Predicted to be involved in protein polyglycylation. Predicted to be located in axoneme and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

TTLL10 links:

TTLL10-AS1 (HGNC:41159): (TTLL10 antisense RNA 1)

TTLL10-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10509515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL10	NM_001130045.2 linkuse as main transcript	c.53C>T	p.Thr18Ile	missense_variant	4/16	ENST00000379289.6	NP_001123517.1
TTLL10-AS1	NR_173246.1 linkuse as main transcript	n.191+97G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL10	ENST00000379289.6 linkuse as main transcript	c.53C>T	p.Thr18Ile	missense_variant	4/16	2	NM_001130045.2	ENSP00000368591	P1	Q6ZVT0-1
TTLL10	ENST00000379290.6 linkuse as main transcript	c.53C>T	p.Thr18Ile	missense_variant	4/16	1		ENSP00000368592	P1	Q6ZVT0-1
TTLL10-AS1	ENST00000379317.1 linkuse as main transcript	n.191+97G>A		intron_variant, non_coding_transcript_variant		2
TTLL10	ENST00000673999.1 linkuse as main transcript	c.53C>T	p.Thr18Ile	missense_variant	4/6			ENSP00000500959

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

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:

0.00000572

AC:

AN:

1398572

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

689792

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:

0.00000649

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.53C>T (p.T18I) alteration is located in exon 4 (coding exon 1) of the TTLL10 gene. This alteration results from a C to T substitution at nucleotide position 53, causing the threonine (T) at amino acid position 18 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0065

T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.39

.;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.042

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.82

P;P

Vest4

0.10

MutPred

0.17

Loss of phosphorylation at T18 (P = 0.0245);Loss of phosphorylation at T18 (P = 0.0245);

MVP

0.23

MPC

0.030

ClinPred

0.16

GERP RS

3.0

Varity_R

0.050

gMVP

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over