rs724743

Positions:

• chr14-75663248-A-G

Variant summary

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

The NM_015072.5(TTLL5):​c.74+25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,599,164 control chromosomes in the GnomAD database, including 152 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 0.017 (96 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (56 hom.)
• Consequence: TTLL5 NM_015072.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495

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]

FLVCR2 (HGNC:20105): (FLVCR choline and putative heme transporter 2) This gene encodes a member of the major facilitator superfamily. The encoded transmembrane protein is a calcium transporter. Unlike the related protein feline leukemia virus subgroup C receptor 1, the protein encoded by this locus does not bind to feline leukemia virus subgroup C envelope protein. The encoded protein may play a role in development of brain vascular endothelial cells, as mutations at this locus have been associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome. Alternatively spliced transcript variants have been described.[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTLL5	NM_015072.5	c.74+25A>G		intron_variant		ENST00000298832.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTLL5	ENST00000298832.14	c.74+25A>G		intron_variant		1	NM_015072.5	P4

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2608 AN: 152194 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00431 AC: 980 AN: 227376 Hom.: 21 AF XY: 0.00327 AC XY: 399 AN XY: 121964

Gnomad AFR exome AF: 0.0612

Gnomad AMR exome AF: 0.00277

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000146

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00175 AC: 2528 AN: 1446852 Hom.: 56 Cov.: 29 AF XY: 0.00152 AC XY: 1090 AN XY: 718656

Gnomad4 AFR exome AF: 0.0606

Gnomad4 AMR exome AF: 0.00342

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000179

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000951

Gnomad4 OTH exome AF: 0.00389

GnomAD4 genome AF: 0.0171 AC: 2611 AN: 152312 Hom.: 96 Cov.: 32 AF XY: 0.0167 AC XY: 1241 AN XY: 74486

Gnomad4 AFR AF: 0.0595

Gnomad4 AMR AF: 0.00641

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00367 Hom.: 12

Bravo AF: 0.0191

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.87

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: rs724743; hg19: chr14-76129591;