1-229602423-T-G

Variant names:

• chr1-229602423-T-G
• rs3753886
• NM_014409.4:c.744A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014409.4(TAF5L):​c.744A>C​(p.Arg248Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,613,782 control chromosomes in the GnomAD database, including 227,411 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 0.54 (22008 hom., cov: 31)
  • Exomes 𝑓: 0.53 (205403 hom.)
• Consequence: TAF5L NM_014409.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.83
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-4.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF5L	NM_014409.4	c.744A>C	p.Arg248Arg	synonymous_variant	Exon 4 of 5	ENST00000258281.7	NP_055224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF5L	ENST00000258281.7	c.744A>C	p.Arg248Arg	synonymous_variant	Exon 4 of 5	5	NM_014409.4	ENSP00000258281.2
TAF5L	ENST00000366675.3	c.744A>C	p.Arg248Arg	synonymous_variant	Exon 4 of 4	1		ENSP00000355635.3

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81218 AN: 151812 Hom.: 21982 Cov.: 31

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.529

GnomAD2 exomes AF: 0.560 AC: 140559 AN: 251022 AF XY: 0.554

Gnomad AFR exome AF: 0.513

Gnomad AMR exome AF: 0.665

Gnomad ASJ exome AF: 0.488

Gnomad EAS exome AF: 0.757

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.511

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.527 AC: 769932 AN: 1461852 Hom.: 205403 Cov.: 74 AF XY: 0.527 AC XY: 383593 AN XY: 727226

African (AFR) AF: 0.511 AC: 17120 AN: 33480

American (AMR) AF: 0.652 AC: 29173 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 12780 AN: 26136

East Asian (EAS) AF: 0.800 AC: 31764 AN: 39700

South Asian (SAS) AF: 0.553 AC: 47720 AN: 86258

European-Finnish (FIN) AF: 0.558 AC: 29801 AN: 53416

Middle Eastern (MID) AF: 0.531 AC: 3062 AN: 5768

European-Non Finnish (NFE) AF: 0.509 AC: 566400 AN: 1111976

Other (OTH) AF: 0.532 AC: 32112 AN: 60396

GnomAD4 genome AF: 0.535 AC: 81301 AN: 151930 Hom.: 22008 Cov.: 31 AF XY: 0.544 AC XY: 40426 AN XY: 74248

African (AFR) AF: 0.513 AC: 21242 AN: 41412

American (AMR) AF: 0.591 AC: 9027 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1710 AN: 3470

East Asian (EAS) AF: 0.768 AC: 3973 AN: 5176

South Asian (SAS) AF: 0.568 AC: 2733 AN: 4808

European-Finnish (FIN) AF: 0.568 AC: 5984 AN: 10530

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34953 AN: 67944

Other (OTH) AF: 0.529 AC: 1115 AN: 2106

Alfa AF: 0.511 Hom.: 22201

Bravo AF: 0.535

Asia WGS AF: 0.632 AC: 2194 AN: 3478

EpiCase AF: 0.516

EpiControl AF: 0.514

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.57
PhyloP100		-4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs3753886; hg19: chr1-229738170; COSMIC: COSV51081759; COSMIC: COSV51081759;