rs759573716

Variant names:

• chr10-103368204-C-A
• rs759573716
• NM_006951.5:c.215C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-103368204-C-A
• chr10-103368204-C-T

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.215C>A​(p.Ala72Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000798 in 1,253,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A72V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: TAF5 NM_006951.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13
• Publications: 0 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=0.12642878).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006951.5. 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
	TAF5	NM_006951.5	MANE Select	c.215C>A	p.Ala72Asp	missense	Exon 1 of 11	NP_008882.2
	TAF5	NM_139052.3		c.215C>A	p.Ala72Asp	missense	Exon 1 of 10	NP_620640.1	Q15542-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF5	ENST00000369839.4	TSL:1 MANE Select	c.215C>A	p.Ala72Asp	missense	Exon 1 of 11	ENSP00000358854.3	Q15542-1
	TAF5	ENST00000940446.1		c.215C>A	p.Ala72Asp	missense	Exon 1 of 10	ENSP00000610505.1
	TAF5	ENST00000692195.1		c.215C>A	p.Ala72Asp	missense	Exon 1 of 10	ENSP00000510076.1	Q15542-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.98e-7 AC: 1 AN: 1253138 Hom.: 0 Cov.: 33 AF XY: 0.00000164 AC XY: 1 AN XY: 609150

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25178

American (AMR) AF: 0.00 AC: 0 AN: 15468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18782

East Asian (EAS) AF: 0.00 AC: 0 AN: 28546

South Asian (SAS) AF: 0.00 AC: 0 AN: 61776

European-Finnish (FIN) AF: 0.0000293 AC: 1 AN: 34160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4614

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1012882

Other (OTH) AF: 0.00 AC: 0 AN: 51732

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.1
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.085
Sift	Uncertain	0.012	D
Sift4G	Benign	0.57	T
Polyphen		0.079	B
Vest4		0.27
MutPred		0.11		Loss of glycosylation at P75 (P = 0.0868)
MVP		0.30
MPC		1.1
ClinPred		0.34	T
GERP RS		2.6
PromoterAI		-0.046	Neutral
Varity_R		0.37
gMVP		0.26
Mutation Taster		=88/12	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: rs759573716; hg19: chr10-105127961;