20-62064842-C-A

Variant names:

• chr20-62064842-C-A
• rs199804789
• NM_003185.4:c.969G>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003185.4(TAF4):​c.969G>T​(p.Ala323Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 965,642 control chromosomes in the GnomAD database, including 21,387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2048 hom., cov: 24)
  • Exomes 𝑓: 0.21 (19339 hom.)
• Consequence: TAF4 NM_003185.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.307
• Publications: 0 publications found

Genes affected

TAF4 (HGNC:11537): (TATA-box binding protein associated factor 4) 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 larger subunits of TFIID that has been shown to potentiate transcriptional activation by retinoic acid, thyroid hormone and vitamin D3 receptors. In addition, this subunit interacts with the transcription factor CREB, which has a glutamine-rich activation domain, and binds to other proteins containing glutamine-rich regions. Aberrant binding to this subunit by proteins with expanded polyglutamine regions has been suggested as one of the pathogenetic mechanisms underlying a group of neurodegenerative disorders referred to as polyglutamine diseases. [provided by RefSeq, Jul 2008]

MIR3195 (HGNC:38250): (microRNA 3195) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ENSG00000283078 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 20-62064842-C-A is Benign according to our data. Variant chr20-62064842-C-A is described in ClinVar as Benign. ClinVar VariationId is 1227169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.307 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003185.4. 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
	TAF4	NM_003185.4	MANE Select	c.969G>T	p.Ala323Ala	synonymous	Exon 1 of 15	NP_003176.2	O00268
	MIR3195	NR_130463.1		n.41C>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF4	ENST00000252996.9	TSL:1 MANE Select	c.969G>T	p.Ala323Ala	synonymous	Exon 1 of 15	ENSP00000252996.3	O00268
	MIR3195	ENST00000585001.1	TSL:6	n.41C>A		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000283078	ENST00000751839.1		n.111+321C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.151 AC: 21145 AN: 139890 Hom.: 2049 Cov.: 24

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0800

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.187

GnomAD2 exomes AF: 0.361 AC: 13 AN: 36 AF XY: 0.417

Gnomad NFE exome AF: 0.361

GnomAD4 exome AF: 0.213 AC: 175952 AN: 825760 Hom.: 19339 Cov.: 21 AF XY: 0.213 AC XY: 81407 AN XY: 381568

African (AFR) AF: 0.0281 AC: 440 AN: 15678

American (AMR) AF: 0.185 AC: 186 AN: 1006

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 1161 AN: 5136

East Asian (EAS) AF: 0.0837 AC: 302 AN: 3606

South Asian (SAS) AF: 0.171 AC: 2859 AN: 16676

European-Finnish (FIN) AF: 0.150 AC: 46 AN: 306

Middle Eastern (MID) AF: 0.266 AC: 428 AN: 1612

European-Non Finnish (NFE) AF: 0.219 AC: 165217 AN: 754702

Other (OTH) AF: 0.197 AC: 5313 AN: 27038

GnomAD4 genome AF: 0.151 AC: 21127 AN: 139882 Hom.: 2048 Cov.: 24 AF XY: 0.147 AC XY: 9984 AN XY: 67896

African (AFR) AF: 0.0443 AC: 1740 AN: 39244

American (AMR) AF: 0.174 AC: 2502 AN: 14354

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 742 AN: 3330

East Asian (EAS) AF: 0.0800 AC: 357 AN: 4460

South Asian (SAS) AF: 0.158 AC: 693 AN: 4396

European-Finnish (FIN) AF: 0.126 AC: 948 AN: 7552

Middle Eastern (MID) AF: 0.260 AC: 67 AN: 258

European-Non Finnish (NFE) AF: 0.213 AC: 13502 AN: 63488

Other (OTH) AF: 0.185 AC: 359 AN: 1940

Alfa AF: 0.170 Hom.: 389

Bravo AF: 0.148

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs199804789; hg19: chr20-60639898; COSMIC: COSV53339934; COSMIC: COSV53339934;