6-167340474-G-C

Variant names:

• chr6-167340474-G-C
• NM_031949.5:c.574G>C
• TTLL2 p.Val192Leu

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.574G>C​(p.Val192Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V192M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTLL2 NM_031949.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• Publications: 0 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=0.16098246).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL2	NM_031949.5	MANE Select	c.574G>C	p.Val192Leu	missense	Exon 3 of 3	NP_114155.4
	TTLL2	NM_001410948.1		c.355G>C	p.Val119Leu	missense	Exon 2 of 2	NP_001397877.1	A0A3B3IRU1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL2	ENST00000239587.10	TSL:1 MANE Select	c.574G>C	p.Val192Leu	missense	Exon 3 of 3	ENSP00000239587.5	Q9BWV7
	TTLL2	ENST00000515138.1	TSL:1	n.574G>C		non_coding_transcript_exon	Exon 3 of 6	ENSP00000424130.1	Q9BWV7
	TTLL2	ENST00000649884.1		c.355G>C	p.Val119Leu	missense	Exon 2 of 2	ENSP00000497040.1	A0A3B3IRU1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.27
DANN	Benign	0.94
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.60	N
PhyloP100		0.14
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.069
Sift	Benign	0.14	T
Sift4G	Benign	0.16	T
Varity_R		0.20
gMVP		0.35
Mutation Taster		=89/11	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-167753962;