Genetic Variant NM_015072.5:c.656-106T>A (chr14-75707517-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015072.5(TTLL5):c.656-106T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 856,848 control chromosomes in the GnomAD database, including 185,211 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 0.60 ( 28706 hom., cov: 30)

Exomes 𝑓: 0.66 ( 156505 hom. )

Consequence

TTLL5
NM_015072.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.783

Publications

10 publications found

Variant links:

Genes affected

TTLL5 (HGNC:19963): (tubulin tyrosine ligase like 5) This gene encodes a member of the tubulin tyrosine ligase like protein family. This protein interacts with two glucocorticoid receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. This protein may function as a coregulator of glucocorticoid receptor mediated gene induction and repression. This protein may also function as an alpha tubulin polyglutamylase.[provided by RefSeq, Feb 2010]

TTLL5 Gene-Disease associations (from GenCC):

cone-rod dystrophy 19
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
inherited retinal dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TTLL5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL5	NM_015072.5 link	c.656-106T>A		intron_variant	Intron 8 of 31	ENST00000298832.14	NP_055887.3	Q6EMB2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL5	ENST00000298832.14 link	c.656-106T>A		intron_variant	Intron 8 of 31	1	NM_015072.5	ENSP00000298832.9		Q6EMB2-1

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

91177

AN:

151726

Hom.:

28691

Cov.:

show subpopulations

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.784

Gnomad AMR

AF:

0.632

Gnomad ASJ

AF:

0.557

Gnomad EAS

AF:

0.380

Gnomad SAS

AF:

0.580

Gnomad FIN

AF:

0.778

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.693

Gnomad OTH

AF:

0.610

GnomAD4 exome

AF:

0.660

AC:

465085

AN:

705006

Hom.:

156505

AF XY:

0.656

AC XY:

240964

AN XY:

367066

show subpopulations

African (AFR)

AF:

0.407

AC:

7105

AN:

17440

American (AMR)

AF:

0.650

AC:

17269

AN:

26550

Ashkenazi Jewish (ASJ)

AF:

0.560

AC:

10125

AN:

18080

East Asian (EAS)

AF:

0.413

AC:

13559

AN:

32868

South Asian (SAS)

AF:

0.582

AC:

32109

AN:

55206

European-Finnish (FIN)

AF:

0.767

AC:

25693

AN:

33490

Middle Eastern (MID)

AF:

0.530

AC:

1527

AN:

2880

European-Non Finnish (NFE)

AF:

0.694

AC:

335541

AN:

483536

Other (OTH)

AF:

0.634

AC:

22157

AN:

34956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

7522

15043

22565

30086

37608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5290

10580

15870

21160

26450

<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:

0.601

AC:

91235

AN:

151842

Hom.:

28706

Cov.:

AF XY:

0.603

AC XY:

44768

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.424

AC:

17527

AN:

41366

American (AMR)

AF:

0.632

AC:

9632

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

1930

AN:

3464

East Asian (EAS)

AF:

0.380

AC:

1967

AN:

5178

South Asian (SAS)

AF:

0.581

AC:

2793

AN:

4804

European-Finnish (FIN)

AF:

0.778

AC:

8195

AN:

10530

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.693

AC:

47050

AN:

67934

Other (OTH)

AF:

0.605

AC:

1278

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1708

3416

5125

6833

8541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

750

1500

2250

3000

3750

<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:

0.649

Hom.:

4141

Bravo

AF:

0.584

Asia WGS

AF:

0.485

AC:

1685

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.36

(source)

DANN

Benign

0.80

PhyloP100

-0.78

Mutation Taster

=12/88

disease causing

(source)

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

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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