Variant chr2-218737817-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014640.5(TTLL4):c.141G>T(p.Gln47His) variant causes a missense change. The variant allele was found at a frequency of 0.0057 in 1,614,222 control chromosomes in the GnomAD database, including 324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 169 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 155 hom. )

Consequence

TTLL4
NM_014640.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.41

Variant links:

Genes affected

TTLL4 (HGNC:28976): (tubulin tyrosine ligase like 4) 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 regulation of blastocyst development. Predicted to be located in cytosol. Predicted to be active in cilium. [provided by Alliance of Genome Resources, Apr 2022]

TTLL4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019230843).

BP6

Variant 2-218737817-G-T is Benign according to our data. Variant chr2-218737817-G-T is described in ClinVar as [Benign]. Clinvar id is 775815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL4	NM_014640.5 linkuse as main transcript	c.141G>T	p.Gln47His	missense_variant	3/20	ENST00000392102.6	NP_055455.3	Q14679A0A024R424

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL4	ENST00000392102.6 linkuse as main transcript	c.141G>T	p.Gln47His	missense_variant	3/20	1	NM_014640.5	ENSP00000375951.1		Q14679

Frequencies

GnomAD3 genomes

AF:

0.0272

AC:

4134

AN:

152210

Hom.:

169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0908

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.00822

AC:

2066

AN:

251252

Hom.:

AF XY:

0.00626

AC XY:

850

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.0941

Gnomad AMR exome

AF:

0.00896

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.00913

GnomAD4 exome

AF:

0.00346

AC:

5061

AN:

1461894

Hom.:

155

Cov.:

AF XY:

0.00314

AC XY:

2283

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0911

Gnomad4 AMR exome

AF:

0.00939

Gnomad4 ASJ exome

AF:

0.00203

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000862

Gnomad4 OTH exome

AF:

0.00823

GnomAD4 genome

AF:

0.0272

AC:

4142

AN:

152328

Hom.:

169

Cov.:

AF XY:

0.0258

AC XY:

1925

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0907

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.00521

Hom.:

Bravo

AF:

0.0311

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0951

AC:

419

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00971

AC:

1179

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00190

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

0.18

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

.;T;.;T;.;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

T;.;T;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;L;.;.;.;L

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-5.0

D;N;D;N;D;N

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.97

.;D;.;D;.;D

Vest4

0.47, 0.55, 0.47

MutPred

0.17

Loss of MoRF binding (P = 0.1017);Loss of MoRF binding (P = 0.1017);Loss of MoRF binding (P = 0.1017);Loss of MoRF binding (P = 0.1017);Loss of MoRF binding (P = 0.1017);Loss of MoRF binding (P = 0.1017);

MVP

0.43

MPC

0.66

ClinPred

0.041

GERP RS

5.3

Varity_R

0.32

gMVP

0.54

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