chr9-121848257-G-A

Position:

• chr9-121848257-G-A

Variant summary

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

The NM_001139442.2(TTLL11):​c.1840+12080C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 151,654 control chromosomes in the GnomAD database, including 24,449 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 0.56 (24449 hom., cov: 31)
• Consequence: TTLL11 NM_001139442.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL11	NM_001139442.2	c.1840+12080C>T		intron_variant		ENST00000321582.11	NP_001132914.2
TTLL11	NM_001386833.1	c.187+12080C>T		intron_variant			NP_001373762.1
TTLL11	XM_047422825.1	c.1264+12080C>T		intron_variant			XP_047278781.1
TTLL11	XR_001746188.2	n.2000+12080C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL11	ENST00000321582.11	c.1840+12080C>T		intron_variant		5	NM_001139442.2	ENSP00000321346	P1
TTLL11	ENST00000373778.5	c.*918+12080C>T		intron_variant, NMD_transcript_variant		5		ENSP00000478392
TTLL11	ENST00000474723.5	c.*1114+12080C>T		intron_variant, NMD_transcript_variant		2		ENSP00000479407
TTLL11	ENST00000687938.1	n.482+12080C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85336 AN: 151542 Hom.: 24429 Cov.: 31

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.563 AC: 85401 AN: 151654 Hom.: 24449 Cov.: 31 AF XY: 0.567 AC XY: 42023 AN XY: 74100

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.537

Alfa AF: 0.575 Hom.: 4274

Bravo AF: 0.542

Asia WGS AF: 0.725 AC: 2525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.72

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: rs10760198; hg19: chr9-124610536;