1-229594705-G-C

Variant names:

• chr1-229594705-G-C
• rs2295625
• NM_014409.4:c.1362C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014409.4(TAF5L):​c.1362C>G​(p.Ser454Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF5L NM_014409.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.876

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014409.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF5L	NM_014409.4	MANE Select	c.1362C>G	p.Ser454Arg	missense	Exon 5 of 5	NP_055224.1	O75529-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF5L	ENST00000258281.7	TSL:5 MANE Select	c.1362C>G	p.Ser454Arg	missense	Exon 5 of 5	ENSP00000258281.2	O75529-1
	TAF5L	ENST00000912671.1		c.1362C>G	p.Ser454Arg	missense	Exon 5 of 5	ENSP00000582730.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 94

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.62
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.14
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.063	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.67		Gain of MoRF binding (P = 0.0175)
MVP		0.93
MPC		1.3
ClinPred		0.94	D
GERP RS		-5.3
Varity_R		0.66
gMVP		0.79
Mutation Taster		=38/62	disease causing

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: rs2295625; hg19: chr1-229730452;