9-121861594-A-G

Position:

• chr9-121861594-A-G

Variant summary

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

The NM_001139442.2(TTLL11):​c.1734-1151T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 151,990 control chromosomes in the GnomAD database, including 36,672 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 0.69 (36672 hom., cov: 31)
• Consequence: TTLL11 NM_001139442.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

Genes affected

TTLL11 (HGNC:18113): (tubulin tyrosine ligase like 11) 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 severing. Predicted to be located in cytosol. Predicted to be active in cilium. [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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTLL11	NM_001139442.2	c.1734-1151T>C		intron_variant		ENST00000321582.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTLL11	ENST00000321582.11	c.1734-1151T>C		intron_variant		5	NM_001139442.2	P1
TTLL11	ENST00000373778.5	c.*812-1151T>C		intron_variant, NMD_transcript_variant		5
TTLL11	ENST00000474723.5	c.*1008-1151T>C		intron_variant, NMD_transcript_variant		2
TTLL11	ENST00000687938.1	n.376-1151T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105187 AN: 151872 Hom.: 36627 Cov.: 31

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.693 AC: 105284 AN: 151990 Hom.: 36672 Cov.: 31 AF XY: 0.692 AC XY: 51409 AN XY: 74290

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.891

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.680

Alfa AF: 0.679 Hom.: 50718

Bravo AF: 0.689

Asia WGS AF: 0.794 AC: 2762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.34

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: rs10739600; hg19: chr9-124623873;