NM_001130918.3:c.603T>C

Variant names:

• chr17-48801263-A-G
• rs17634167
• NM_001130918.3:c.603T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001130918.3(TTLL6):​c.603T>C​(p.Leu201Leu) 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
• Publications: 12 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 -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.

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.603T>C	p.Leu201Leu	synonymous	Exon 5 of 16	NP_001124390.1	Q8N841-1
	TTLL6	NM_001366314.2		c.144T>C	p.Leu48Leu	synonymous	Exon 5 of 14	NP_001353243.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL6	ENST00000393382.8	TSL:2 MANE Select	c.603T>C	p.Leu201Leu	synonymous	Exon 5 of 16	ENSP00000377043.3	Q8N841-1
	TTLL6	ENST00000376681.7	TSL:1	n.*646T>C		non_coding_transcript_exon	Exon 5 of 14	ENSP00000365871.4	F8WDP8
	TTLL6	ENST00000490027.5	TSL:1	n.1427T>C		non_coding_transcript_exon	Exon 4 of 16

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

GnomAD2 exomes AF: 0.0921 AC: 14376 AN: 156150 AF XY: 0.0911

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 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

African (AFR) AF: 0.0383 AC: 1211 AN: 31594

American (AMR) AF: 0.0549 AC: 1960 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.0782 AC: 1970 AN: 25176

East Asian (EAS) AF: 0.0441 AC: 1575 AN: 35728

South Asian (SAS) AF: 0.0357 AC: 2827 AN: 79236

European-Finnish (FIN) AF: 0.133 AC: 6573 AN: 49282

Middle Eastern (MID) AF: 0.0755 AC: 430 AN: 5694

European-Non Finnish (NFE) AF: 0.133 AC: 143794 AN: 1078648

Other (OTH) AF: 0.102 AC: 5895 AN: 57996

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

African (AFR) AF: 0.0419 AC: 1742 AN: 41530

American (AMR) AF: 0.0695 AC: 1062 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3470

East Asian (EAS) AF: 0.0580 AC: 300 AN: 5176

South Asian (SAS) AF: 0.0365 AC: 176 AN: 4818

European-Finnish (FIN) AF: 0.133 AC: 1406 AN: 10590

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.134 AC: 9080 AN: 68006

Other (OTH) AF: 0.114 AC: 239 AN: 2104

Alfa AF: 0.114 Hom.: 1919

Bravo AF: 0.0879

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.9
DANN	Benign	0.68
PhyloP100		-0.53
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17634167; hg19: chr17-46878625; COSMIC: COSV64977412; COSMIC: COSV64977412;