22-43168808-G-A

Variant names:

• chr22-43168808-G-A
• rs145496614
• NM_015140.4:c.1749C>T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_015140.4(TTLL12):​c.1749C>T​(p.Val583Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00554 in 1,577,448 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0057 (31 hom.)
• Consequence: TTLL12 NM_015140.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.297

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 22-43168808-G-A is Benign according to our data. Variant chr22-43168808-G-A is described in ClinVar as [Benign]. Clinvar id is 784893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.297 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL12	NM_015140.4	c.1749C>T	p.Val583Val	synonymous_variant	Exon 13 of 14	ENST00000216129.7	NP_055955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL12	ENST00000216129.7	c.1749C>T	p.Val583Val	synonymous_variant	Exon 13 of 14	1	NM_015140.4	ENSP00000216129.6
TTLL12	ENST00000494035.1	c.12C>T	p.Val4Val	synonymous_variant	Exon 3 of 4	2		ENSP00000476297.1
TTLL12	ENST00000484711.1	n.880C>T		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.00449 AC: 683 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00744

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00440 AC: 840 AN: 190780 Hom.: 2 AF XY: 0.00476 AC XY: 488 AN XY: 102442

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00245

Gnomad ASJ exome AF: 0.00963

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00223

Gnomad FIN exome AF: 0.000489

Gnomad NFE exome AF: 0.00704

Gnomad OTH exome AF: 0.00557

GnomAD4 exome AF: 0.00565 AC: 8059 AN: 1425114 Hom.: 31 Cov.: 31 AF XY: 0.00575 AC XY: 4060 AN XY: 705628

Gnomad4 AFR exome AF: 0.000798

Gnomad4 AMR exome AF: 0.00244

Gnomad4 ASJ exome AF: 0.00999

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00221

Gnomad4 FIN exome AF: 0.000754

Gnomad4 NFE exome AF: 0.00651

Gnomad4 OTH exome AF: 0.00515

GnomAD4 genome AF: 0.00450 AC: 685 AN: 152334 Hom.: 0 Cov.: 33 AF XY: 0.00375 AC XY: 279 AN XY: 74474

Gnomad4 AFR AF: 0.00128

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00744

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00632 Hom.: 4

Bravo AF: 0.00449

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 07, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	3.9
DANN	Benign	0.91

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

LitVar

Other links and lift over

dbSNP: rs145496614; hg19: chr22-43564814; COSMIC: COSV53357052;