Variant chr6-167338772-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_031949.5(TTLL2):c.173G>A(p.Arg58Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,613,140 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

TTLL2
NM_031949.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.620

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 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=0.019102901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL2	NM_031949.5 linkuse as main transcript	c.173G>A	p.Arg58Gln	missense_variant	2/3	ENST00000239587.10	NP_114155.4	Q9BWV7
TTLL2	NM_001410948.1 linkuse as main transcript	c.-15-1333G>A		intron_variant			NP_001397877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TTLL2	ENST00000239587.10 linkuse as main transcript	c.173G>A	p.Arg58Gln	missense_variant	2/3	1	NM_031949.5	ENSP00000239587.5	Q9BWV7
TTLL2	ENST00000515138.1 linkuse as main transcript	n.173G>A		non_coding_transcript_exon_variant	2/6	1		ENSP00000424130.1	Q9BWV7
TTLL2	ENST00000649884.1 linkuse as main transcript	c.-15-1333G>A		intron_variant				ENSP00000497040.1	A0A3B3IRU1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000443

AC:

AN:

248564

Hom.:

AF XY:

0.0000521

AC XY:

AN XY:

134418

show subpopulations

Gnomad AFR exome

AF:

0.0000623

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:

0.0000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000431

AC:

AN:

1460918

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

726732

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000522

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000124

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Nov 14, 2024

The c.173G>A (p.R58Q) alteration is located in exon 2 (coding exon 2) of the TTLL2 gene. This alteration results from a G to A substitution at nucleotide position 173, causing the arginine (R) at amino acid position 58 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

0.093

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

DANN

Benign

0.84

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0034

M_CAP

Benign

0.00073

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.070

REVEL

Benign

0.0010

Sift

Benign

0.12

Sift4G

Benign

0.26

Polyphen

0.0020

Vest4

0.065

MVP

0.014

MPC

0.14

ClinPred

0.012

GERP RS

-3.1

Varity_R

0.022

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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