rs13058467

Variant names:

• chr22-43183043-T-C
• rs13058467
• NM_015140.4:c.284A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015140.4(TTLL12):​c.284A>G​(p.Asn95Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 1,613,948 control chromosomes in the GnomAD database, including 8,588 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.088 (661 hom., cov: 33)
  • Exomes 𝑓: 0.099 (7927 hom.)
• Consequence: TTLL12 NM_015140.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 29 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014352798).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL12	NM_015140.4	MANE Select	c.284A>G	p.Asn95Ser	missense	Exon 2 of 14	NP_055955.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL12	ENST00000216129.7	TSL:1 MANE Select	c.284A>G	p.Asn95Ser	missense	Exon 2 of 14	ENSP00000216129.6

Frequencies

GnomAD3 genomes AF: 0.0879 AC: 13365 AN: 152126 Hom.: 661 Cov.: 33

Gnomad AFR AF: 0.0732

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.0794

Gnomad ASJ AF: 0.0819

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.0802 AC: 20156 AN: 251168 AF XY: 0.0806

Gnomad AFR exome AF: 0.0707

Gnomad AMR exome AF: 0.0562

Gnomad ASJ exome AF: 0.0838

Gnomad EAS exome AF: 0.000653

Gnomad FIN exome AF: 0.0882

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.0969

GnomAD4 exome AF: 0.0988 AC: 144349 AN: 1461704 Hom.: 7927 Cov.: 32 AF XY: 0.0977 AC XY: 71071 AN XY: 727158

African (AFR) AF: 0.0728 AC: 2437 AN: 33478

American (AMR) AF: 0.0599 AC: 2677 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 2132 AN: 26134

East Asian (EAS) AF: 0.000479 AC: 19 AN: 39700

South Asian (SAS) AF: 0.0540 AC: 4656 AN: 86258

European-Finnish (FIN) AF: 0.0840 AC: 4478 AN: 53300

Middle Eastern (MID) AF: 0.100 AC: 578 AN: 5768

European-Non Finnish (NFE) AF: 0.109 AC: 121743 AN: 1111964

Other (OTH) AF: 0.0932 AC: 5629 AN: 60386

GnomAD4 genome AF: 0.0879 AC: 13377 AN: 152244 Hom.: 661 Cov.: 33 AF XY: 0.0853 AC XY: 6348 AN XY: 74438

African (AFR) AF: 0.0732 AC: 3039 AN: 41534

American (AMR) AF: 0.0792 AC: 1212 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0819 AC: 284 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.0427 AC: 206 AN: 4830

European-Finnish (FIN) AF: 0.0814 AC: 864 AN: 10616

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7357 AN: 68002

Other (OTH) AF: 0.0993 AC: 210 AN: 2114

Alfa AF: 0.0994 Hom.: 2689

Bravo AF: 0.0883

TwinsUK AF: 0.110 AC: 407

ALSPAC AF: 0.120 AC: 462

ESP6500AA AF: 0.0726 AC: 320

ESP6500EA AF: 0.108 AC: 930

ExAC AF: 0.0797 AC: 9673

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.20
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.044	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.23	N
PhyloP100		0.19
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.043
Sift	Benign	0.88	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.018
MPC		0.072
ClinPred		0.00029	T
GERP RS		0.063
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.019
gMVP		0.19
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13058467; hg19: chr22-43579049; COSMIC: COSV53354417;