17-48763179-T-G

Variant names:

• chr17-48763179-T-G
• rs7219021
• NM_001130918.3:c.*1-206A>C

Variant summary

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

The NM_001130918.3(TTLL6):​c.*1-206A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,924 control chromosomes in the GnomAD database, including 5,121 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 0.26 (5121 hom., cov: 31)
• Consequence: TTLL6 NM_001130918.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.828

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL6	NM_001130918.3	c.*1-206A>C		intron_variant	Intron 15 of 15	ENST00000393382.8	NP_001124390.1
TTLL6	NM_173623.4	c.*1-206A>C		intron_variant	Intron 8 of 8		NP_775894.2
TTLL6	NM_001366314.2	c.1582-206A>C		intron_variant	Intron 13 of 13		NP_001353243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL6	ENST00000393382.8	c.*1-206A>C		intron_variant	Intron 15 of 15	2	NM_001130918.3	ENSP00000377043.3

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38954 AN: 151806 Hom.: 5114 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.257 AC: 38985 AN: 151924 Hom.: 5121 Cov.: 31 AF XY: 0.257 AC XY: 19100 AN XY: 74254

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.264

Alfa AF: 0.263 Hom.: 5098

Bravo AF: 0.269

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.70

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: rs7219021; hg19: chr17-46840541;