rs1005224

Positions:

• chr14-75707517-T-A

Variant summary

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

The NM_015072.5(TTLL5):​c.656-106T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 856,848 control chromosomes in the GnomAD database, including 185,211 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 0.60 (28706 hom., cov: 30)
  • Exomes 𝑓: 0.66 (156505 hom.)
• Consequence: TTLL5 NM_015072.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783

Genes affected

TTLL5 (HGNC:19963): (tubulin tyrosine ligase like 5) This gene encodes a member of the tubulin tyrosine ligase like protein family. This protein interacts with two glucocorticoid receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. This protein may function as a coregulator of glucocorticoid receptor mediated gene induction and repression. This protein may also function as an alpha tubulin polyglutamylase.[provided by RefSeq, Feb 2010]

TTLL5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL5	NM_015072.5	c.656-106T>A		intron_variant		ENST00000298832.14	NP_055887.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL5	ENST00000298832.14	c.656-106T>A		intron_variant		1	NM_015072.5	ENSP00000298832.9

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91177 AN: 151726 Hom.: 28691 Cov.: 30

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.610

GnomAD4 exome AF: 0.660 AC: 465085 AN: 705006 Hom.: 156505 AF XY: 0.656 AC XY: 240964 AN XY: 367066

Gnomad4 AFR exome AF: 0.407

Gnomad4 AMR exome AF: 0.650

Gnomad4 ASJ exome AF: 0.560

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.582

Gnomad4 FIN exome AF: 0.767

Gnomad4 NFE exome AF: 0.694

Gnomad4 OTH exome AF: 0.634

GnomAD4 genome AF: 0.601 AC: 91235 AN: 151842 Hom.: 28706 Cov.: 30 AF XY: 0.603 AC XY: 44768 AN XY: 74204

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.605

Alfa AF: 0.649 Hom.: 4141

Bravo AF: 0.584

Asia WGS AF: 0.485 AC: 1685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.36
DANN	Benign	0.80

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: rs1005224; hg19: chr14-76173860; COSMIC: COSV54030123;