chr14-75773491-G-A

Variant names:

• chr14-75773491-G-A
• rs7161217
• NM_015072.5:c.2136+1637G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 19

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000309804 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015072.5. 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
	TTLL5	NM_015072.5	MANE Select	c.2136+1637G>A		intron	N/A	NP_055887.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL5	ENST00000298832.14	TSL:1 MANE Select	c.2136+1637G>A		intron	N/A	ENSP00000298832.9
	TTLL5	ENST00000557636.5	TSL:1	c.2178+1637G>A		intron	N/A	ENSP00000450713.1
	TTLL5	ENST00000556893.5	TSL:1	c.789+1637G>A		intron	N/A	ENSP00000452524.1

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

African (AFR) AF: 0.732 AC: 30344 AN: 41450

American (AMR) AF: 0.805 AC: 12312 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2289 AN: 3470

East Asian (EAS) AF: 0.535 AC: 2763 AN: 5162

South Asian (SAS) AF: 0.735 AC: 3539 AN: 4818

European-Finnish (FIN) AF: 0.873 AC: 9213 AN: 10556

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52834 AN: 67990

Other (OTH) AF: 0.740 AC: 1565 AN: 2114

Alfa AF: 0.729 Hom.: 3346

Bravo AF: 0.754

Asia WGS AF: 0.677 AC: 2352 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	0.63
DANN	Benign	0.55
PhyloP100		0.41
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: rs7161217; hg19: chr14-76239834;