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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015140.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL12	NM_015140.4	MANE Select	c.*1185C>A		3_prime_UTR	Exon 14 of 14	NP_055955.1	Q14166

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL12	ENST00000216129.7	TSL:1 MANE Select	c.*1185C>A		3_prime_UTR	Exon 14 of 14	ENSP00000216129.6	Q14166
	TTLL12	ENST00000484711.1	TSL:2	n.2251C>A		non_coding_transcript_exon	Exon 3 of 3

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over