20-62064838-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003185.4(TAF4):​c.973G>C​(p.Val325Leu) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V325F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Consequence

TAF4
NM_003185.4 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.079104245).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TAF4NM_003185.4 linkc.973G>C p.Val325Leu missense_variant Exon 1 of 15 ENST00000252996.9 NP_003176.2 O00268
TAF4XM_047440429.1 linkc.-144G>C 5_prime_UTR_variant Exon 2 of 16 XP_047296385.1
MIR3195NR_130463.1 linkn.37C>G non_coding_transcript_exon_variant Exon 1 of 1
MIR3195unassigned_transcript_3472 n.*10C>G downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TAF4ENST00000252996.9 linkc.973G>C p.Val325Leu missense_variant Exon 1 of 15 1 NM_003185.4 ENSP00000252996.3 O00268
MIR3195ENST00000585001.1 linkn.37C>G non_coding_transcript_exon_variant Exon 1 of 1 6

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
Cov.:
22
GnomAD4 genome
Cov.:
24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
13
DANN
Benign
0.49
DEOGEN2
Benign
0.088
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.27
T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.079
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.85
N
REVEL
Benign
0.052
Sift
Uncertain
0.0070
D
Sift4G
Benign
0.19
T
Polyphen
0.0
B
Vest4
0.090
MutPred
0.23
Loss of sheet (P = 0.1398);
MVP
0.12
MPC
0.68
ClinPred
0.21
T
GERP RS
0.38
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.095
gMVP
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1369654553; hg19: chr20-60639894; API