rs10465746

chr1-83921949-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024686.6(TTLL7):c.1143-555A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,948 control chromosomes in the GnomAD database, including 15,863 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (15863 hom., cov: 32)
• Consequence: TTLL7 NM_024686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTLL7	NM_024686.6	c.1143-555A>C		intron_variant		ENST00000260505.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTLL7	ENST00000260505.13	c.1143-555A>C		intron_variant		2	NM_024686.6	P1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66601 AN: 151830 Hom.: 15853 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.445

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.438 AC: 66625 AN: 151948 Hom.: 15863 Cov.: 32 AF XY: 0.435 AC XY: 32296 AN XY: 74236

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.440

Alfa AF: 0.481 Hom.: 3585

Bravo AF: 0.436

Asia WGS AF: 0.323 AC: 1122 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.6
Dann	Benign	0.66

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: rs10465746; hg19: chr1-84387632;