17-48763179-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130918.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL6	NM_001130918.3	MANE Select	c.*1-206A>C		intron	N/A	NP_001124390.1	Q8N841-1
	TTLL6	NM_173623.4		c.*1-206A>C		intron	N/A	NP_775894.2	A0AAA9X7X9
	TTLL6	NM_001366314.2		c.1582-206A>C		intron	N/A	NP_001353243.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL6	ENST00000393382.8	TSL:2 MANE Select	c.*1-206A>C		intron	N/A	ENSP00000377043.3	Q8N841-1
	TTLL6	ENST00000433608.6	TSL:1	c.*1-206A>C		intron	N/A	ENSP00000399211.2	A0AAA9X7X9
	TTLL6	ENST00000376681.7	TSL:1	n.*2084-206A>C		intron	N/A	ENSP00000365871.4	F8WDP8

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

African (AFR) AF: 0.236 AC: 9768 AN: 41448

American (AMR) AF: 0.381 AC: 5805 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3466

East Asian (EAS) AF: 0.167 AC: 863 AN: 5168

South Asian (SAS) AF: 0.179 AC: 858 AN: 4798

European-Finnish (FIN) AF: 0.219 AC: 2312 AN: 10552

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17477 AN: 67940

Other (OTH) AF: 0.264 AC: 558 AN: 2112

Alfa AF: 0.264 Hom.: 6199

Bravo AF: 0.269

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.70
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism (auto)

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: rs7219021; hg19: chr17-46840541;