rs17634167

chr17-48801263-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001130918.3(TTLL6):c.603T>C(p.Leu201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,551,240 control chromosomes in the GnomAD database, including 11,502 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 0.095 (872 hom., cov: 31)
  • Exomes 𝑓: 0.12 (10630 hom.)
• Consequence: TTLL6 NM_001130918.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-0.527 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTLL6	NM_001130918.3	c.603T>C	p.Leu201=	synonymous_variant	5/16	ENST00000393382.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTLL6	ENST00000393382.8	c.603T>C	p.Leu201=	synonymous_variant	5/16	2	NM_001130918.3	P1
TTLL6	ENST00000490027.5	n.1427T>C		non_coding_transcript_exon_variant	4/16	1
TTLL6	ENST00000376681.7	c.*646T>C		3_prime_UTR_variant, NMD_transcript_variant	5/14	1
TTLL6	ENST00000509809.1	n.338T>C		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14401 AN: 152068 Hom.: 871 Cov.: 31

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.0576

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.114

GnomAD3 exomes AF: 0.0921 AC: 14376 AN: 156150 Hom.: 850 AF XY: 0.0911 AC XY: 7537 AN XY: 82762

Gnomad AFR exome AF: 0.0353

Gnomad AMR exome AF: 0.0532

Gnomad ASJ exome AF: 0.0823

Gnomad EAS exome AF: 0.0684

Gnomad SAS exome AF: 0.0353

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.0947

GnomAD4 exome AF: 0.119 AC: 166235 AN: 1399054 Hom.: 10630 Cov.: 33 AF XY: 0.116 AC XY: 80278 AN XY: 690006

Gnomad4 AFR exome AF: 0.0383

Gnomad4 AMR exome AF: 0.0549

Gnomad4 ASJ exome AF: 0.0782

Gnomad4 EAS exome AF: 0.0441

Gnomad4 SAS exome AF: 0.0357

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.0946 AC: 14403 AN: 152186 Hom.: 872 Cov.: 31 AF XY: 0.0914 AC XY: 6796 AN XY: 74390

Gnomad4 AFR AF: 0.0419

Gnomad4 AMR AF: 0.0695

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.0580

Gnomad4 SAS AF: 0.0365

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.114

Alfa AF: 0.111 Hom.: 459

Bravo AF: 0.0879

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	4.9
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs17634167; hg19: chr17-46878625; COSMIC: COSV64977412; COSMIC: COSV64977412;