chr9-121994289-C-T

Variant names:

• chr9-121994289-C-T
• rs4836873
• NM_001139442.2:c.694-4519G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001139442.2(TTLL11):​c.694-4519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,894 control chromosomes in the GnomAD database, including 14,797 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 0.42 (14797 hom., cov: 31)
• Consequence: TTLL11 NM_001139442.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 2 publications found

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

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 = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001139442.2. 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
	TTLL11	NM_001139442.2	MANE Select	c.694-4519G>A		intron	N/A	NP_001132914.2	Q8NHH1-1
	TTLL11	NM_001386831.1		c.694-4519G>A		intron	N/A	NP_001373760.1
	TTLL11	NM_194252.3		c.694-4519G>A		intron	N/A	NP_919228.3	Q8NHH1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL11	ENST00000321582.11	TSL:5 MANE Select	c.694-4519G>A		intron	N/A	ENSP00000321346.6	Q8NHH1-1
	TTLL11	ENST00000373776.5	TSL:1	c.694-4519G>A		intron	N/A	ENSP00000362881.4	Q8NHH1-2
	TTLL11	ENST00000487468.5	TSL:1	c.176-4519G>A		intron	N/A	ENSP00000478658.1	A0A087WUG8

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63274 AN: 151776 Hom.: 14753 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.0903

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.417 AC: 63394 AN: 151894 Hom.: 14797 Cov.: 31 AF XY: 0.415 AC XY: 30767 AN XY: 74220

African (AFR) AF: 0.629 AC: 26059 AN: 41414

American (AMR) AF: 0.321 AC: 4893 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3464

East Asian (EAS) AF: 0.0905 AC: 467 AN: 5158

South Asian (SAS) AF: 0.220 AC: 1058 AN: 4812

European-Finnish (FIN) AF: 0.430 AC: 4529 AN: 10534

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23924 AN: 67934

Other (OTH) AF: 0.391 AC: 824 AN: 2106

Alfa AF: 0.387 Hom.: 1990

Bravo AF: 0.419

Asia WGS AF: 0.207 AC: 725 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	0.22
DANN	Benign	0.59
PhyloP100		-1.2
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: rs4836873; hg19: chr9-124756568;