17-48805683-C-T

Variant summary

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

The NM_001130918.3(TTLL6):c.104-692G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,184 control chromosomes in the GnomAD database, including 1,948 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 0.15 (1948 hom., cov: 32)
• Consequence: TTLL6 NM_001130918.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

Genes affected

TTLL6 (HGNC:26664): (tubulin tyrosine ligase like 6) 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 act upstream of or within microtubule bundle formation; microtubule severing; and positive regulation of cilium movement. Located in ciliary basal body. [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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTLL6	NM_001130918.3	c.104-692G>A		intron_variant		ENST00000393382.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTLL6	ENST00000393382.8	c.104-692G>A		intron_variant		2	NM_001130918.3	P1
TTLL6	ENST00000376681.7	c.109-692G>A		intron_variant, NMD_transcript_variant		1
TTLL6	ENST00000490027.5	n.85-692G>A		intron_variant, non_coding_transcript_variant		1
TTLL6	ENST00000456415.1	c.*22-692G>A		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22775 AN: 152066 Hom.: 1945 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0909

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.0591

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.150 AC: 22792 AN: 152184 Hom.: 1948 Cov.: 32 AF XY: 0.145 AC XY: 10811 AN XY: 74392

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.0907

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.0595

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.152

Alfa AF: 0.125 Hom.: 1802

Bravo AF: 0.148

Asia WGS AF: 0.111 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	3.7
Dann	Benign	0.79

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: rs8073596; hg19: chr17-46883045;