Variant 17-48770002-C-A 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_001130918.3(TTLL6):c.2136G>T(p.Glu712Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,613,782 control chromosomes in the GnomAD database, including 54,844 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5353 hom., cov: 31)

Exomes 𝑓: 0.26 ( 49491 hom. )

Consequence

TTLL6
NM_001130918.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.63

Variant links:

Genes affected

TTLL6 (HGNC:26664): (tubulin tyrosine ligase like 6) 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 bundle formation; microtubule severing; and positive regulation of cilium movement. Located in ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

TTLL6 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=0.0027991235).

BP6

Variant 17-48770002-C-A is Benign according to our data. Variant chr17-48770002-C-A is described in ClinVar as [Benign]. Clinvar id is 1263302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL6	NM_001130918.3 linkuse as main transcript	c.2136G>T	p.Glu712Asp	missense_variant	14/16	ENST00000393382.8	NP_001124390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL6	ENST00000393382.8 linkuse as main transcript	c.2136G>T	p.Glu712Asp	missense_variant	14/16	2	NM_001130918.3	ENSP00000377043	P1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39839

AN:

151792

Hom.:

5345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.156

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.268

GnomAD3 exomes

AF:

0.260

AC:

65480

AN:

251398

Hom.:

9197

AF XY:

0.254

AC XY:

34551

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.304

Gnomad EAS exome

AF:

0.167

Gnomad SAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.223

Gnomad NFE exome

AF:

0.252

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.257

AC:

375606

AN:

1461872

Hom.:

49491

Cov.:

AF XY:

0.254

AC XY:

184973

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.261

Gnomad4 AMR exome

AF:

0.397

Gnomad4 ASJ exome

AF:

0.304

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.226

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.262

AC:

39876

AN:

151910

Hom.:

5353

Cov.:

AF XY:

0.263

AC XY:

19514

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.257

Gnomad4 AMR

AF:

0.384

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.156

Gnomad4 SAS

AF:

0.178

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.257

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.256

Hom.:

12961

Bravo

AF:

0.276

TwinsUK

AF:

0.261

AC:

967

ALSPAC

AF:

0.268

AC:

1033

ESP6500AA

AF:

0.258

AC:

1137

ESP6500EA

AF:

0.249

AC:

2144

ExAC

AF:

0.253

AC:

30711

Asia WGS

AF:

0.175

AC:

612

AN:

3478

EpiCase

AF:

0.264

EpiControl

AF:

0.260

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	GeneDx	Jul 13, 2018	This variant is associated with the following publications: (PMID: 29632382) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

3.9

DANN

Uncertain

1.0

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.014

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

REVEL

Benign

0.24

Sift4G

Uncertain

0.034

D;T

Vest4

0.097

MPC

0.46

ClinPred

0.056

GERP RS

-3.8

gMVP

0.14

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