Variant 9-121822717-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_001139442.2(TTLL11):c.2003C>T(p.Ser668Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,398,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

TTLL11
NM_001139442.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.216

Variant links:

Genes affected

TTLL11 (HGNC:18113): (tubulin tyrosine ligase like 11) Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule cytoskeleton organization and protein polyglutamylation. Predicted to act upstream of or within microtubule severing. Predicted to be located in cytosol. Predicted to be active in cilium. [provided by Alliance of Genome Resources, Apr 2022]

TTLL11 links:

TTLL11 (HGNC:):

TTLL11 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=0.06291467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL11	NM_001139442.2 linkuse as main transcript	c.2003C>T	p.Ser668Leu	missense_variant	9/9	ENST00000321582.11	NP_001132914.2	Q8NHH1Q6ZUZ3
TTLL11	NM_001386833.1 linkuse as main transcript	c.350C>T	p.Ser117Leu	missense_variant	4/4		NP_001373762.1
TTLL11	XM_047422825.1 linkuse as main transcript	c.1427C>T	p.Ser476Leu	missense_variant	8/8		XP_047278781.1
TTLL11	XR_001746188.2 linkuse as main transcript	n.2163C>T		non_coding_transcript_exon_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL11	ENST00000321582.11 linkuse as main transcript	c.2003C>T	p.Ser668Leu	missense_variant	9/9	5	NM_001139442.2	ENSP00000321346.6		Q8NHH1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

152910

Hom.:

AF XY:

0.0000492

AC XY:

AN XY:

81332

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000440

Gnomad FIN exome

AF:

0.0000655

Gnomad NFE exome

AF:

0.0000339

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1398576

Hom.:

Cov.:

AF XY:

0.0000232

AC XY:

AN XY:

689788

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.0000204

Gnomad4 NFE exome

AF:

0.0000176

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 09, 2021

The c.2273C>T (p.S758L) alteration is located in exon 9 (coding exon 9) of the TTLL11 gene. This alteration results from a C to T substitution at nucleotide position 2273, causing the serine (S) at amino acid position 758 to be replaced by a leucine (L). 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

0.075

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.8

DANN

Benign

0.60

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.45

M_CAP

Benign

0.020

MetaRNN

Benign

0.063

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.44

PROVEAN

Benign

0.050

REVEL

Benign

0.018

Sift

Benign

0.040

Sift4G

Uncertain

0.053

Vest4

0.051

MutPred

0.17

Loss of glycosylation at S758 (P = 0.0051);

MVP

0.11

MPC

0.52

ClinPred

0.061

GERP RS

0.96

Varity_R

0.034

gMVP

0.11

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