9-122014825-C-T

Variant names:

• chr9-122014825-C-T
• rs10985483
• NM_001139442.2:c.693+16898G>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.693+16898G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,914 control chromosomes in the GnomAD database, including 16,155 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 0.43 (16155 hom., cov: 31)
• Consequence: TTLL11 NM_001139442.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL11	NM_001139442.2	MANE Select	c.693+16898G>A		intron	N/A	NP_001132914.2
	TTLL11	NM_001386831.1		c.693+16898G>A		intron	N/A	NP_001373760.1
	TTLL11	NM_194252.3		c.693+16898G>A		intron	N/A	NP_919228.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL11	ENST00000321582.11	TSL:5 MANE Select	c.693+16898G>A		intron	N/A	ENSP00000321346.6
	TTLL11	ENST00000373776.5	TSL:1	c.693+16898G>A		intron	N/A	ENSP00000362881.4
	TTLL11	ENST00000487468.5	TSL:1	c.175+24447G>A		intron	N/A	ENSP00000478658.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65659 AN: 151796 Hom.: 16101 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.0869

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.433 AC: 65790 AN: 151914 Hom.: 16155 Cov.: 31 AF XY: 0.430 AC XY: 31944 AN XY: 74228

African (AFR) AF: 0.669 AC: 27684 AN: 41406

American (AMR) AF: 0.372 AC: 5675 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3468

East Asian (EAS) AF: 0.0871 AC: 450 AN: 5168

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4812

European-Finnish (FIN) AF: 0.430 AC: 4544 AN: 10556

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23926 AN: 67928

Other (OTH) AF: 0.405 AC: 852 AN: 2106

Alfa AF: 0.393 Hom.: 2847

Bravo AF: 0.441

Asia WGS AF: 0.211 AC: 740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.046
DANN	Benign	0.42
PhyloP100		-1.8
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: rs10985483; hg19: chr9-124777104;