Variant 1-1179249-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001130045.2(TTLL10):c.34C>T(p.Arg12Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,550,008 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R12P) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TTLL10
NM_001130045.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.969

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 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=0.06652179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL10	NM_001130045.2 link	c.34C>T	p.Arg12Trp	missense_variant	4/16	ENST00000379289.6	NP_001123517.1	Q6ZVT0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TTLL10	ENST00000379289.6 link	c.34C>T	p.Arg12Trp	missense_variant	4/16	2	NM_001130045.2	ENSP00000368591.1	Q6ZVT0-1
TTLL10	ENST00000379290.6 link	c.34C>T	p.Arg12Trp	missense_variant	4/16	1		ENSP00000368592.1	Q6ZVT0-1
TTLL10	ENST00000673999.1 link	c.34C>T	p.Arg12Trp	missense_variant	4/6			ENSP00000500959.1	A0A669K9N4
TTLL10-AS1	ENST00000379317.1 link	n.191+116G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000394

AC:

AN:

152256

Hom.:

AF XY:

0.0000495

AC XY:

AN XY:

80866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000408

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000276

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000343

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1397788

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

689340

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.0000281

Gnomad4 ASJ exome

AF:

0.0000399

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000111

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

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

Jun 03, 2022

The c.34C>T (p.R12W) 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 34, causing the arginine (R) at amino acid position 12 to be replaced by a tryptophan (W). 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

-0.47

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0063

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.63

.;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

L;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.015

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.035

B;B

Vest4

0.13

MutPred

0.34

Loss of methylation at R17 (P = 0.0244);Loss of methylation at R17 (P = 0.0244);

MVP

0.13

MPC

0.028

ClinPred

0.035

GERP RS

-0.22

Varity_R

0.057

gMVP

0.20

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