NM_001130918.3:c.104-692G>A

Variant names:

• chr17-48805683-C-T
• rs8073596
• NM_001130918.3:c.104-692G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 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.104-692G>A		intron	N/A	NP_001124390.1	Q8N841-1
	TTLL6	NM_001366314.2		c.-951-692G>A		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.104-692G>A		intron	N/A	ENSP00000377043.3	Q8N841-1
	TTLL6	ENST00000376681.7	TSL:1	n.107-692G>A		intron	N/A	ENSP00000365871.4	F8WDP8
	TTLL6	ENST00000456415.1	TSL:4	n.*22-692G>A		intron	N/A	ENSP00000414290.1	F6QD81

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

African (AFR) AF: 0.221 AC: 9159 AN: 41502

American (AMR) AF: 0.0907 AC: 1387 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3470

East Asian (EAS) AF: 0.0595 AC: 308 AN: 5180

South Asian (SAS) AF: 0.135 AC: 652 AN: 4830

European-Finnish (FIN) AF: 0.132 AC: 1399 AN: 10592

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9161 AN: 68002

Other (OTH) AF: 0.152 AC: 322 AN: 2112

Alfa AF: 0.128 Hom.: 2614

Bravo AF: 0.148

Asia WGS AF: 0.111 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.79
PhyloP100		0.0090
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: rs8073596; hg19: chr17-46883045;