Variant 6-167340505-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000239587.10(TTLL2):c.605T>C(p.Leu202Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 1,614,136 control chromosomes in the GnomAD database, including 235 homozygotes. 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 Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.022 ( 138 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 97 hom. )

Consequence

TTLL2
ENST00000239587.10 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.173

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022521317).

BP6

Variant 6-167340505-T-C is Benign according to our data. Variant chr6-167340505-T-C is described in ClinVar as [Benign]. Clinvar id is 780669.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0736 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.605T>C	p.Leu202Pro	missense_variant	3/3	ENST00000239587.10	NP_114155.4	Q9BWV7
TTLL2	NM_001410948.1 linkuse as main transcript	c.386T>C	p.Leu129Pro	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.605T>C	p.Leu202Pro	missense_variant	3/3	1	NM_031949.5	ENSP00000239587.5	Q9BWV7
TTLL2	ENST00000515138.1 linkuse as main transcript	n.605T>C		non_coding_transcript_exon_variant	3/6	1		ENSP00000424130.1	Q9BWV7
TTLL2	ENST00000649884.1 linkuse as main transcript	c.386T>C	p.Leu129Pro	missense_variant	2/2			ENSP00000497040.1	A0A3B3IRU1

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3320

AN:

152126

Hom.:

137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0759

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00759

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00571

AC:

1435

AN:

251426

Hom.:

AF XY:

0.00412

AC XY:

560

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0771

Gnomad AMR exome

AF:

0.00373

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00235

AC:

3435

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

1423

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0766

Gnomad4 AMR exome

AF:

0.00445

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000277

Gnomad4 OTH exome

AF:

0.00518

GnomAD4 genome

AF:

0.0219

AC:

3328

AN:

152242

Hom.:

138

Cov.:

AF XY:

0.0213

AC XY:

1584

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0758

Gnomad4 AMR

AF:

0.00758

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00973

Hom.:

Bravo

AF:

0.0243

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0749

AC:

330

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00707

AC:

858

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.2

DANN

Benign

0.41

DEOGEN2

Benign

0.017

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.30

T;.

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.3

.;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.85

.;N

REVEL

Benign

0.019

Sift

Benign

0.29

.;T

Sift4G

Benign

0.29

.;T

Polyphen

0.0020

.;B

Vest4

0.16

MVP

0.014

MPC

0.23

ClinPred

0.0017

GERP RS

-0.35

Varity_R

0.20

gMVP

0.62

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