6-167341487-G-C

Variant names:

• chr6-167341487-G-C
• rs12528714
• NM_031949.5:c.1587G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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: not found (cov: 31)
• Consequence: TTLL2 NM_031949.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 12 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031949.5. 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
	TTLL2	NM_031949.5	MANE Select	c.1587G>C	p.Gln529His	missense	Exon 3 of 3	NP_114155.4
	TTLL2	NM_001410948.1		c.1368G>C	p.Gln456His	missense	Exon 2 of 2	NP_001397877.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL2	ENST00000239587.10	TSL:1 MANE Select	c.1587G>C	p.Gln529His	missense	Exon 3 of 3	ENSP00000239587.5
	TTLL2	ENST00000515138.1	TSL:1	n.1587G>C		non_coding_transcript_exon	Exon 3 of 6	ENSP00000424130.1
	TTLL2	ENST00000649884.1		c.1368G>C	p.Gln456His	missense	Exon 2 of 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 v4.9

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
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.97	L
PhyloP100		-0.60
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
Mutation Taster		=100/0	polymorphism

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: rs12528714; hg19: chr6-167754975;