rs369610870

Variant names:

• chr10-103368246-C-A
• rs369610870
• NM_006951.5:c.257C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-103368246-C-A
• chr10-103368246-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006951.5(TAF5):​c.257C>A​(p.Pro86Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000297 in 1,347,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P86L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: TAF5 NM_006951.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05676648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF5	NM_006951.5	c.257C>A	p.Pro86Gln	missense_variant	Exon 1 of 11	ENST00000369839.4	NP_008882.2
TAF5	NM_139052.3	c.257C>A	p.Pro86Gln	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.257C>A	p.Pro86Gln	missense_variant	Exon 1 of 11	1	NM_006951.5	ENSP00000358854.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000323 AC: 4 AN: 123802 AF XY: 0.0000283

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000123

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000297 AC: 4 AN: 1347758 Hom.: 0 Cov.: 33 AF XY: 0.00000301 AC XY: 2 AN XY: 663984

African (AFR) AF: 0.00 AC: 0 AN: 28264

American (AMR) AF: 0.00 AC: 0 AN: 30210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23336

East Asian (EAS) AF: 0.0000310 AC: 1 AN: 32254

South Asian (SAS) AF: 0.0000396 AC: 3 AN: 75816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5090

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1061318

Other (OTH) AF: 0.00 AC: 0 AN: 55880

GnomAD4 genome Cov.: 33

Alfa AF: 0.000248 Hom.: 0

Asia WGS AF: 0.000290 AC: 1 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.080
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.037	D
Polyphen		0.0010	B
Vest4		0.086
MutPred		0.067		Loss of glycosylation at P86 (P = 0.0764);
MVP		0.18
MPC		0.76
ClinPred		0.13	T
GERP RS		2.5
PromoterAI		-0.038	Neutral
Varity_R		0.11
gMVP		0.15
Mutation Taster		=97/3	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: rs369610870; hg19: chr10-105128003;