rs397509359

Variant names:

• chrX-71529785-C-T
• rs397509359
• ENST00000437147.8:n.*247C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-71529785-C-T
• chrX-71529785-C-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000437147.8(TAF1):​n.*247C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000276 in 326,523 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000033 (0 hom. 1 hem.)
• Consequence: TAF1 ENST00000437147.8 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:2
• Conservation: PhyloP100: -4.11
• Publications: 3 publications found

Genes affected

TAF1 (HGNC:11535): (TATA-box binding protein associated factor 1) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is the basal transcription factor TFIID, which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes the largest subunit of TFIID. This subunit binds to core promoter sequences encompassing the transcription start site. It also binds to activators and other transcriptional regulators, and these interactions affect the rate of transcription initiation. This subunit contains two independent protein kinase domains at the N- and C-terminals, but also possesses acetyltransferase activity and can act as a ubiquitin-activating/conjugating enzyme. Mutations in this gene result in Dystonia 3, torsion, X-linked, a dystonia-parkinsonism disorder. Alternative splicing of this gene results in multiple transcript variants. This gene is part of a complex transcription unit (TAF1/DYT3), wherein some transcript variants share exons with TAF1 as well as additional downstream DYT3 exons. [provided by RefSeq, Oct 2013]

SOCS6P1 (HGNC:54990): (SOCS6 pseudogene 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000437147.8. 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
	TAF1	NR_104387.2		n.5776C>T		non_coding_transcript_exon	Exon 40 of 40
	TAF1	NR_104388.2		n.5767C>T		non_coding_transcript_exon	Exon 40 of 40
	TAF1	NR_104389.2		n.5674C>T		non_coding_transcript_exon	Exon 39 of 39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1	ENST00000437147.8	TSL:1	n.*247C>T		non_coding_transcript_exon	Exon 14 of 14	ENSP00000406517.4	H7C2K9
	TAF1	ENST00000462588.5	TSL:1	n.*247C>T		non_coding_transcript_exon	Exon 11 of 11	ENSP00000508350.1	A0A804HLH3
	TAF1	ENST00000467309.5	TSL:1	n.*363C>T		non_coding_transcript_exon	Exon 5 of 6	ENSP00000507353.1	A0A804HJ48

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112177 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000279

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000327 AC: 7 AN: 214346 Hom.: 0 Cov.: 0 AF XY: 0.0000120 AC XY: 1 AN XY: 83302

African (AFR) AF: 0.00 AC: 0 AN: 6785

American (AMR) AF: 0.00 AC: 0 AN: 21033

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7819

East Asian (EAS) AF: 0.00 AC: 0 AN: 6590

South Asian (SAS) AF: 0.00 AC: 0 AN: 34613

European-Finnish (FIN) AF: 0.000205 AC: 2 AN: 9744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2045

European-Non Finnish (NFE) AF: 0.0000260 AC: 3 AN: 115264

Other (OTH) AF: 0.000191 AC: 2 AN: 10453

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112177 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34325

African (AFR) AF: 0.00 AC: 0 AN: 30864

American (AMR) AF: 0.00 AC: 0 AN: 10600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.000279 AC: 1 AN: 3582

South Asian (SAS) AF: 0.00 AC: 0 AN: 2701

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6073

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53260

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	1	-	X-linked dystonia-parkinsonism (2)
-	1	-	TAF1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.53
DANN	Benign	0.55
PhyloP100		-4.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs397509359; hg19: chrX-70749635;