rs12528714

Positions:

• chr6-167341487-G-C
• chr6-167341487-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031949.5(TTLL2):​c.1587G>C​(p.Gln529His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TTLL2 NM_031949.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

Genes affected

TTLL2 (HGNC:21211): (tubulin tyrosine ligase like 2) Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule cytoskeleton organization and protein polyglutamylation. Predicted to be active in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.100666165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL2	NM_031949.5	c.1587G>C	p.Gln529His	missense_variant	3/3	ENST00000239587.10	NP_114155.4
TTLL2	NM_001410948.1	c.1368G>C	p.Gln456His	missense_variant	2/2		NP_001397877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL2	ENST00000239587.10	c.1587G>C	p.Gln529His	missense_variant	3/3	1	NM_031949.5	ENSP00000239587.5
TTLL2	ENST00000515138.1	n.1587G>C		non_coding_transcript_exon_variant	3/6	1		ENSP00000424130.1
TTLL2	ENST00000649884.1	c.1368G>C	p.Gln456His	missense_variant	2/2			ENSP00000497040.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0077	.;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.40	T;.
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.97	.;L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.8	.;N
REVEL	Benign	0.022
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.021	.;D
Polyphen		0.98	.;D
Vest4		0.039
MutPred		0.25		.;Gain of catalytic residue at Q529 (P = 0.0214);
MVP		0.092
MPC		0.44
ClinPred		0.33	T
GERP RS		0.78
Varity_R		0.11
gMVP		0.32

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: rs12528714; hg19: chr6-167754975;