rs4252228

Variant names:

• chr5-69366309-G-A
• rs4252228
• NM_003187.5:c.-18+194C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003187.5(TAF9):​c.-18+194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,076 control chromosomes in the GnomAD database, including 10,255 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 0.34 (10255 hom., cov: 32)
• Consequence: TAF9 NM_003187.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 11 publications found

Genes affected

TAF9 (HGNC:11542): (TATA-box binding protein associated factor 9) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (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 one of the smaller subunits of TFIID that binds to the basal transcription factor GTF2B as well as to several transcriptional activators such as p53 and VP16. In human, TAF9 and AK6 (GeneID: 102157402) are two distinct genes that share 5' exons. A similar but distinct gene (TAF9L) has been found on the X chromosome and a pseudogene has been identified on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

AK6 (HGNC:49151): (adenylate kinase 6) This gene encodes a protein that belongs to the adenylate kinase family of enzymes. The protein has a nuclear localization and contains Walker A (P-loop) and Walker B motifs and a metal-coordinating residue. The protein may be involved in regulation of Cajal body formation. In human, AK6 and TAF9 (GeneID: 6880) are two distinct genes that share 5' exons. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF9	NM_003187.5	c.-18+194C>T		intron_variant	Intron 2 of 2	ENST00000217893.10	NP_003178.1
AK6	NM_016283.5	c.121+194C>T		intron_variant	Intron 2 of 4	ENST00000380822.9	NP_057367.1
TAF9	NM_001015892.2	c.-18+194C>T		intron_variant	Intron 2 of 2		NP_001015892.1
AK6	NM_001015891.2	c.112+194C>T		intron_variant	Intron 2 of 4		NP_001015891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF9	ENST00000217893.10	c.-18+194C>T		intron_variant	Intron 2 of 2	1	NM_003187.5	ENSP00000217893.7
AK6	ENST00000380822.9	c.121+194C>T		intron_variant	Intron 2 of 4	1	NM_016283.5	ENSP00000370201.4

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51640 AN: 151958 Hom.: 10258 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.372

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.339 AC: 51624 AN: 152076 Hom.: 10255 Cov.: 32 AF XY: 0.334 AC XY: 24841 AN XY: 74324

African (AFR) AF: 0.128 AC: 5307 AN: 41514

American (AMR) AF: 0.325 AC: 4959 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1242 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2102 AN: 5166

South Asian (SAS) AF: 0.290 AC: 1398 AN: 4826

European-Finnish (FIN) AF: 0.400 AC: 4218 AN: 10542

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31184 AN: 67972

Other (OTH) AF: 0.368 AC: 777 AN: 2110

Alfa AF: 0.413 Hom.: 14475

Bravo AF: 0.330

Asia WGS AF: 0.314 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.24
DANN	Benign	0.53
PhyloP100		0.19

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: rs4252228; hg19: chr5-68662136;