Variant 6-167341487-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031949.5(TTLL2):c.1587G>T(p.Gln529His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,614,076 control chromosomes in the GnomAD database, including 1,329 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.027 ( 122 hom., cov: 31)

Exomes 𝑓: 0.028 ( 1207 hom. )

Consequence

TTLL2
NM_031949.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.602

Variant links:

Genes affected

TTLL2 (HGNC:21211): (tubulin tyrosine ligase like 2) 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 be active in cilium. [provided by Alliance of Genome Resources, Apr 2022]

TTLL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017136633).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL2	NM_031949.5 linkuse as main transcript	c.1587G>T	p.Gln529His	missense_variant	3/3	ENST00000239587.10	NP_114155.4	Q9BWV7
TTLL2	NM_001410948.1 linkuse as main transcript	c.1368G>T	p.Gln456His	missense_variant	2/2		NP_001397877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TTLL2	ENST00000239587.10 linkuse as main transcript	c.1587G>T	p.Gln529His	missense_variant	3/3	1	NM_031949.5	ENSP00000239587.5	Q9BWV7
TTLL2	ENST00000515138.1 linkuse as main transcript	n.1587G>T		non_coding_transcript_exon_variant	3/6	1		ENSP00000424130.1	Q9BWV7
TTLL2	ENST00000649884.1 linkuse as main transcript	c.1368G>T	p.Gln456His	missense_variant	2/2			ENSP00000497040.1	A0A3B3IRU1

Frequencies

GnomAD3 genomes

AF:

0.0274

AC:

4165

AN:

152072

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00998

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.0592

Gnomad SAS

AF:

0.0234

Gnomad FIN

AF:

0.0305

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0197

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0427

AC:

10749

AN:

251470

Hom.:

654

AF XY:

0.0377

AC XY:

5123

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00787

Gnomad AMR exome

AF:

0.170

Gnomad ASJ exome

AF:

0.0133

Gnomad EAS exome

AF:

0.0503

Gnomad SAS exome

AF:

0.0226

Gnomad FIN exome

AF:

0.0283

Gnomad NFE exome

AF:

0.0191

Gnomad OTH exome

AF:

0.0336

GnomAD4 exome

AF:

0.0280

AC:

40984

AN:

1461886

Hom.:

1207

Cov.:

AF XY:

0.0271

AC XY:

19685

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00717

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.0152

Gnomad4 EAS exome

AF:

0.0700

Gnomad4 SAS exome

AF:

0.0221

Gnomad4 FIN exome

AF:

0.0300

Gnomad4 NFE exome

AF:

0.0225

Gnomad4 OTH exome

AF:

0.0286

GnomAD4 genome

AF:

0.0274

AC:

4175

AN:

152190

Hom.:

122

Cov.:

AF XY:

0.0293

AC XY:

2178

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00995

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.0596

Gnomad4 SAS

AF:

0.0235

Gnomad4 FIN

AF:

0.0305

Gnomad4 NFE

AF:

0.0197

Gnomad4 OTH

AF:

0.0422

Alfa

AF:

0.0266

Hom.:

Bravo

AF:

0.0342

TwinsUK

AF:

0.0243

AC:

ALSPAC

AF:

0.0231

AC:

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.0194

AC:

167

ExAC

AF:

0.0366

AC:

4443

Asia WGS

AF:

0.0610

AC:

213

AN:

3478

EpiCase

AF:

0.0173

EpiControl

AF:

0.0168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.5

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0077

.;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.40

T;.

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.97

.;L

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.8

.;N

REVEL

Benign

0.022

Sift

Uncertain

0.0020

.;D

Sift4G

Uncertain

0.021

.;D

Polyphen

0.98

.;D

Vest4

0.039

MutPred

0.25

.;Gain of catalytic residue at Q529 (P = 0.0214);

MPC

0.44

ClinPred

0.021

GERP RS

0.78

Varity_R

0.11

gMVP

0.32

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over