1-83906430-G-T

Variant names:

• chr1-83906430-G-T
• rs781048786
• NM_024686.6:c.2026C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024686.6(TTLL7):​c.2026C>A​(p.Gln676Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. Q676E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTLL7 NM_024686.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.33
• Publications: 2 publications found

Genes affected

TTLL7 (HGNC:26242): (tubulin tyrosine ligase like 7) Enables alpha-tubulin binding activity; beta-tubulin binding activity; and tubulin-glutamic acid ligase activity. Involved in protein polyglutamylation. Predicted to be located in 9+0 non-motile cilium and ciliary basal body. 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=0.14158398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL7	NM_024686.6	c.2026C>A	p.Gln676Lys	missense_variant	Exon 17 of 21	ENST00000260505.13	NP_078962.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL7	ENST00000260505.13	c.2026C>A	p.Gln676Lys	missense_variant	Exon 17 of 21	2	NM_024686.6	ENSP00000260505.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.12
Sift	Benign	0.14	T
Sift4G	Benign	0.17	T
Polyphen		0.35	B
Vest4		0.42
MutPred		0.21		Gain of ubiquitination at Q676 (P = 0.0077);
MVP		0.25
MPC		0.73
ClinPred		0.45	T
GERP RS		3.8
Varity_R		0.25
gMVP		0.46
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs781048786; hg19: chr1-84372113;