Genetic Variant TTLL6:p.Leu201Leu (chr17-48801263-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001130918.3(TTLL6):c.603T>C(p.Leu201Leu) 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

Publications

12 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TTLL6	NM_001130918.3 link	c.603T>C	p.Leu201Leu	synonymous_variant	Exon 5 of 16	ENST00000393382.8	NP_001124390.1	Q8N841

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL6	ENST00000393382.8 link	c.603T>C	p.Leu201Leu	synonymous_variant	Exon 5 of 16	2	NM_001130918.3	ENSP00000377043.3		Q8N841

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

GnomAD2 exomes

AF:

0.0921

AC:

14376

AN:

156150

AF XY:

0.0911

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 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

African (AFR)

AF:

0.0383

AC:

1211

AN:

31594

American (AMR)

AF:

0.0549

AC:

1960

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.0782

AC:

1970

AN:

25176

East Asian (EAS)

AF:

0.0441

AC:

1575

AN:

35728

South Asian (SAS)

AF:

0.0357

AC:

2827

AN:

79236

European-Finnish (FIN)

AF:

0.133

AC:

6573

AN:

49282

Middle Eastern (MID)

AF:

0.0755

AC:

430

AN:

5694

European-Non Finnish (NFE)

AF:

0.133

AC:

143794

AN:

1078648

Other (OTH)

AF:

0.102

AC:

5895

AN:

57996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

7015

14030

21045

28060

35075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5138

10276

15414

20552

25690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0946

AC:

14403

AN:

152186

Hom.:

872

Cov.:

AF XY:

0.0914

AC XY:

6796

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0419

AC:

1742

AN:

41530

American (AMR)

AF:

0.0695

AC:

1062

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0764

AC:

265

AN:

3470

East Asian (EAS)

AF:

0.0580

AC:

300

AN:

5176

South Asian (SAS)

AF:

0.0365

AC:

176

AN:

4818

European-Finnish (FIN)

AF:

0.133

AC:

1406

AN:

10590

Middle Eastern (MID)

AF:

0.0959

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.134

AC:

9080

AN:

68006

Other (OTH)

AF:

0.114

AC:

239

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

646

1292

1939

2585

3231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.114

Hom.:

1919

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

(source)

DANN

Benign

0.68

PhyloP100

-0.53

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over