Genetic Variant TTLL12:c.*1185C>A (chr22-43166823-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015140.4(TTLL12):c.*1185C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 176,574 control chromosomes in the GnomAD database, including 12,756 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 0.37 ( 10889 hom., cov: 33)

Exomes 𝑓: 0.36 ( 1867 hom. )

Consequence

TTLL12
NM_015140.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.364

Publications

17 publications found

Variant links:

Genes affected

TTLL12 (HGNC:28974): (tubulin tyrosine ligase like 12) Enables H4K20me3 modified histone binding activity and tubulin binding activity. Involved in negative regulation of type I interferon-mediated signaling pathway and regulation of mitotic cell cycle. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TTLL12 links:

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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=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL12	NM_015140.4 link	c.*1185C>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000216129.7	NP_055955.1	Q14166A0A024R4U3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL12	ENST00000216129.7 link	c.*1185C>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_015140.4	ENSP00000216129.6		Q14166
TTLL12	ENST00000484711.1 link	n.2251C>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56162

AN:

151982

Hom.:

10879

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.385

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.00656

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.395

GnomAD4 exome

AF:

0.362

AC:

8858

AN:

24474

Hom.:

1867

Cov.:

AF XY:

0.349

AC XY:

4616

AN XY:

13220

show subpopulations

African (AFR)

AF:

0.319

AC:

132

AN:

414

American (AMR)

AF:

0.373

AC:

115

AN:

308

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

221

AN:

542

East Asian (EAS)

AF:

0.00

AC:

AN:

658

South Asian (SAS)

AF:

0.285

AC:

1420

AN:

4986

European-Finnish (FIN)

AF:

0.361

AC:

644

AN:

1782

Middle Eastern (MID)

AF:

0.411

AC:

AN:

European-Non Finnish (NFE)

AF:

0.403

AC:

5840

AN:

14480

Other (OTH)

AF:

0.371

AC:

463

AN:

1248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

271

541

812

1082

1353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.370

AC:

56204

AN:

152100

Hom.:

10889

Cov.:

AF XY:

0.364

AC XY:

27094

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.349

AC:

14469

AN:

41474

American (AMR)

AF:

0.409

AC:

6252

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.424

AC:

1470

AN:

3468

East Asian (EAS)

AF:

0.00677

AC:

AN:

5170

South Asian (SAS)

AF:

0.271

AC:

1307

AN:

4828

European-Finnish (FIN)

AF:

0.347

AC:

3677

AN:

10590

Middle Eastern (MID)

AF:

0.449

AC:

131

AN:

292

European-Non Finnish (NFE)

AF:

0.407

AC:

27691

AN:

67966

Other (OTH)

AF:

0.389

AC:

822

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1827

3654

5480

7307

9134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

0.391

Hom.:

25793

Bravo

AF:

0.373

Asia WGS

AF:

0.155

AC:

542

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.36

(source)

DANN

Benign

0.59

PhyloP100

-0.36

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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