Variant 1-1179235-G-A 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.20G>A(p.Arg7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,548,428 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

TTLL10
NM_001130045.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.09

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=0.059185773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL10	NM_001130045.2 link	c.20G>A	p.Arg7Gln	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.20G>A	p.Arg7Gln	missense_variant	4/16	2	NM_001130045.2	ENSP00000368591.1	Q6ZVT0-1
TTLL10	ENST00000379290.6 link	c.20G>A	p.Arg7Gln	missense_variant	4/16	1		ENSP00000368592.1	Q6ZVT0-1
TTLL10	ENST00000673999.1 link	c.20G>A	p.Arg7Gln	missense_variant	4/6			ENSP00000500959.1	A0A669K9N4
TTLL10-AS1	ENST00000379317.1 link	n.191+130C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152200

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000332

AC:

AN:

150798

Hom.:

AF XY:

0.0000125

AC XY:

AN XY:

80064

show subpopulations

Gnomad AFR exome

AF:

0.000254

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000522

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1396228

Hom.:

Cov.:

AF XY:

0.0000247

AC XY:

AN XY:

688448

show subpopulations

Gnomad4 AFR exome

AF:

0.0000951

Gnomad4 AMR exome

AF:

0.0000282

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000205

Gnomad4 NFE exome

AF:

0.0000325

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74360

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000330

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000409

AC:

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

May 11, 2022

The c.20G>A (p.R7Q) alteration is located in exon 4 (coding exon 1) of the TTLL10 gene. This alteration results from a G to A substitution at nucleotide position 20, causing the arginine (R) at amino acid position 7 to be replaced by a glutamine (Q). 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

0.10

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.3

DANN

Benign

0.97

DEOGEN2

Benign

0.0077

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.44

.;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.70

N;N

REVEL

Benign

0.032

Sift

Benign

0.033

D;D

Sift4G

Uncertain

0.035

D;D

Polyphen

0.86

P;P

Vest4

0.076

MutPred

0.19

Loss of MoRF binding (P = 0.0034);Loss of MoRF binding (P = 0.0034);

MVP

0.11

MPC

0.029

ClinPred

0.011

GERP RS

-2.0

Varity_R

0.029

gMVP

0.049

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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