rs7161217

Positions:

• chr14-75773491-G-A
• chr14-75773491-G-C

Variant summary

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

The NM_015072.5(TTLL5):​c.2136+1637G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,052 control chromosomes in the GnomAD database, including 44,405 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 0.76 (44405 hom., cov: 31)
• Consequence: TTLL5 NM_015072.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL5	NM_015072.5	c.2136+1637G>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.2136+1637G>A		intron_variant		1	NM_015072.5	ENSP00000298832	P4

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115766 AN: 151934 Hom.: 44379 Cov.: 31

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.762 AC: 115845 AN: 152052 Hom.: 44405 Cov.: 31 AF XY: 0.765 AC XY: 56829 AN XY: 74332

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.740

Alfa AF: 0.730 Hom.: 3144

Bravo AF: 0.754

Asia WGS AF: 0.677 AC: 2352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.63
DANN	Benign	0.55

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: rs7161217; hg19: chr14-76239834;