Variant 17-48801263-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001130918.3(TTLL6):c.603T>C(p.Leu201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,551,240 control chromosomes in the GnomAD database, including 11,502 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.095 ( 872 hom., cov: 31)

Exomes 𝑓: 0.12 ( 10630 hom. )

Consequence

TTLL6
NM_001130918.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.527

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP7

Synonymous conserved (PhyloP=-0.527 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 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.603T>C	p.Leu201=	synonymous_variant	5/16	ENST00000393382.8	NP_001124390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TTLL6	ENST00000393382.8 linkuse as main transcript	c.603T>C	p.Leu201=	synonymous_variant	5/16	2	NM_001130918.3	ENSP00000377043	P1
TTLL6	ENST00000490027.5 linkuse as main transcript	n.1427T>C		non_coding_transcript_exon_variant	4/16	1
TTLL6	ENST00000376681.7 linkuse as main transcript	c.*646T>C		3_prime_UTR_variant, NMD_transcript_variant	5/14	1		ENSP00000365871
TTLL6	ENST00000509809.1 linkuse as main transcript	n.338T>C		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes

AF:

0.0947

AC:

14401

AN:

152068

Hom.:

871

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0420

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0696

Gnomad ASJ

AF:

0.0764

Gnomad EAS

AF:

0.0576

Gnomad SAS

AF:

0.0367

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.0892

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.0921

AC:

14376

AN:

156150

Hom.:

850

AF XY:

0.0911

AC XY:

7537

AN XY:

82762

show subpopulations

Gnomad AFR exome

AF:

0.0353

Gnomad AMR exome

AF:

0.0532

Gnomad ASJ exome

AF:

0.0823

Gnomad EAS exome

AF:

0.0684

Gnomad SAS exome

AF:

0.0353

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.0947

GnomAD4 exome

AF:

0.119

AC:

166235

AN:

1399054

Hom.:

10630

Cov.:

AF XY:

0.116

AC XY:

80278

AN XY:

690006

show subpopulations

Gnomad4 AFR exome

AF:

0.0383

Gnomad4 AMR exome

AF:

0.0549

Gnomad4 ASJ exome

AF:

0.0782

Gnomad4 EAS exome

AF:

0.0441

Gnomad4 SAS exome

AF:

0.0357

Gnomad4 FIN exome

AF:

0.133

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.102

GnomAD4 genome

AF:

0.0946

AC:

14403

AN:

152186

Hom.:

872

Cov.:

AF XY:

0.0914

AC XY:

6796

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0419

Gnomad4 AMR

AF:

0.0695

Gnomad4 ASJ

AF:

0.0764

Gnomad4 EAS

AF:

0.0580

Gnomad4 SAS

AF:

0.0365

Gnomad4 FIN

AF:

0.133

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.111

Hom.:

459

Bravo

AF:

0.0879

Asia WGS

AF:

0.0550

AC:

189

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.9

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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