rs2295625

chr1-229594705-G-Achr1-229594705-G-Cchr1-229594705-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014409.4(TAF5L):c.1362C>T(p.Ser454=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,613,918 control chromosomes in the GnomAD database, including 156,422 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 0.36 (11204 hom., cov: 32)
  • Exomes 𝑓: 0.44 (145218 hom.)
• Consequence: TAF5L NM_014409.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

Genes affected

TAF5L (HGNC:17304): (TATA-box binding protein associated factor 5 like) The product of this gene belongs to the WD-repeat TAF5 family of proteins. This gene encodes a protein that is a component of the PCAF histone acetylase complex. The PCAF histone acetylase complex, which is composed of more than 20 polypeptides some of which are TAFs, is required for myogenic transcription and differentiation. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors to facilitate complex assembly and transcription initiation. The encoded protein is structurally similar to one of the histone-like TAFs, TAF5. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=0.139 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF5L	NM_014409.4	c.1362C>T	p.Ser454=	synonymous_variant	5/5	ENST00000258281.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF5L	ENST00000258281.7	c.1362C>T	p.Ser454=	synonymous_variant	5/5	5	NM_014409.4	P1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54156 AN: 151944 Hom.: 11203 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.377

GnomAD3 exomes AF: 0.397 AC: 99747 AN: 251242 Hom.: 21308 AF XY: 0.408 AC XY: 55402 AN XY: 135842

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.417

Gnomad EAS exome AF: 0.323

Gnomad SAS exome AF: 0.414

Gnomad FIN exome AF: 0.465

Gnomad NFE exome AF: 0.467

Gnomad OTH exome AF: 0.423

GnomAD4 exome AF: 0.440 AC: 643821 AN: 1461856 Hom.: 145218 Cov.: 94 AF XY: 0.442 AC XY: 321583 AN XY: 727226

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.415

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.464

Gnomad4 OTH exome AF: 0.419

GnomAD4 genome AF: 0.356 AC: 54174 AN: 152062 Hom.: 11204 Cov.: 32 AF XY: 0.358 AC XY: 26598 AN XY: 74320

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.380

Alfa AF: 0.440 Hom.: 24906

Bravo AF: 0.330

Asia WGS AF: 0.359 AC: 1247 AN: 3478

EpiCase AF: 0.468

EpiControl AF: 0.465

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	0.99
Dann	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs2295625; hg19: chr1-229730452; COSMIC: COSV51080363; COSMIC: COSV51080363;