1-83890357-C-G

Variant names:

• chr1-83890357-C-G
• rs146805080
• NM_024686.6:c.2333G>C

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.2333G>C​(p.Arg778Pro) 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. 14/22 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. R778H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTLL7 NM_024686.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.07
• Publications: 9 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=0.19932696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL7	NM_024686.6	c.2333G>C	p.Arg778Pro	missense_variant	Exon 19 of 21	ENST00000260505.13	NP_078962.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL7	ENST00000260505.13	c.2333G>C	p.Arg778Pro	missense_variant	Exon 19 of 21	2	NM_024686.6	ENSP00000260505.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.1
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.15	B
Vest4		0.48
MutPred		0.47		Loss of MoRF binding (P = 0.0123);
MVP		0.22
MPC		0.85
ClinPred		0.85	D
GERP RS		2.8
Varity_R		0.41
gMVP		0.67
Mutation Taster		=93/7	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: rs146805080; hg19: chr1-84356040;