chr10-103368303-G-A

Variant names:

• chr10-103368303-G-A
• rs1385582047
• NM_006951.5:c.314G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006951.5(TAF5):​c.314G>A​(p.Arg105Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,431,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TAF5 NM_006951.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.46
• Publications: 1 publications found

Genes affected

TAF5 (HGNC:11539): (TATA-box binding protein associated factor 5) 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 an integral subunit of TFIID associated with all transcriptionally competent forms of that complex. This subunit interacts strongly with two TFIID subunits that show similarity to histones H3 and H4, and it may participate in forming a nucleosome-like core in the TFIID complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21521538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF5	NM_006951.5	c.314G>A	p.Arg105Gln	missense_variant	Exon 1 of 11	ENST00000369839.4	NP_008882.2
TAF5	NM_139052.3	c.314G>A	p.Arg105Gln	missense_variant	Exon 1 of 10		NP_620640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF5	ENST00000369839.4	c.314G>A	p.Arg105Gln	missense_variant	Exon 1 of 11	1	NM_006951.5	ENSP00000358854.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 200294 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000279 AC: 4 AN: 1431800 Hom.: 0 Cov.: 34 AF XY: 0.00000422 AC XY: 3 AN XY: 711484

African (AFR) AF: 0.00 AC: 0 AN: 32642

American (AMR) AF: 0.00 AC: 0 AN: 42500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25596

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38748

South Asian (SAS) AF: 0.00 AC: 0 AN: 83564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5536

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1105834

Other (OTH) AF: 0.00 AC: 0 AN: 59634

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.314G>A (p.R105Q) alteration is located in exon 1 (coding exon 1) of the TAF5 gene. This alteration results from a G to A substitution at nucleotide position 314, causing the arginine (R) at amino acid position 105 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	0.0030	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.5
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.059
Sift	Uncertain	0.010	D
Sift4G	Benign	0.095	T
Polyphen		0.80	P
Vest4		0.11
MutPred		0.18		Loss of MoRF binding (P = 0.0223);
MVP		0.64
MPC		0.97
ClinPred		0.89	D
GERP RS		4.3
PromoterAI		0.018	Neutral
Varity_R		0.29
gMVP		0.27
Mutation Taster		=83/17	polymorphism

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: rs1385582047; hg19: chr10-105128060;