rs1320565

Positions:

• chr1-1184478-C-T

Variant summary

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

The NM_001130045.2(TTLL10):​c.1260+387C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,114 control chromosomes in the GnomAD database, including 9,350 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 0.25 (9350 hom., cov: 32)
• Consequence: TTLL10 NM_001130045.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25

Genes affected

TTLL10 (HGNC:26693): (tubulin tyrosine ligase like 10) Predicted to enable protein-glycine ligase activity, elongating. Predicted to be involved in protein polyglycylation. Predicted to be located in axoneme and microtubule cytoskeleton. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL10	NM_001130045.2	c.1260+387C>T		intron_variant		ENST00000379289.6	NP_001123517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL10	ENST00000379289.6	c.1260+387C>T		intron_variant		2	NM_001130045.2	ENSP00000368591	P1
TTLL10	ENST00000379288.3	c.1041+387C>T		intron_variant		1		ENSP00000368590
TTLL10	ENST00000379290.6	c.1260+387C>T		intron_variant		1		ENSP00000368592	P1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38613 AN: 151996 Hom.: 9316 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.254 AC: 38707 AN: 152114 Hom.: 9350 Cov.: 32 AF XY: 0.255 AC XY: 18976 AN XY: 74376

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0739

Gnomad4 OTH AF: 0.230

Alfa AF: 0.127 Hom.: 1508

Bravo AF: 0.273

Asia WGS AF: 0.292 AC: 1012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.85
DANN	Benign	0.75

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: rs1320565; hg19: chr1-1119858; COSMIC: COSV64961363; COSMIC: COSV64961363;