10-7964043-A-G

Position:

• chr10-7964043-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031923.4(TAF3):​c.533A>G​(p.Lys178Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TAF3 NM_031923.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.85

Genes affected

TAF3 (HGNC:17303): (TATA-box binding protein associated factor 3) The highly conserved RNA polymerase II transcription factor TFIID (see TAF1; MIM 313650) comprises the TATA box-binding protein (TBP; MIM 600075) and a set of TBP-associated factors (TAFs), including TAF3. TAFs contribute to promoter recognition and selectivity and act as antiapoptotic factors (Gangloff et al., 2001 [PubMed 11438666]).[supplied by OMIM, May 2009]

TAF3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF3	NM_031923.4	c.533A>G	p.Lys178Arg	missense_variant	3/7	ENST00000344293.6	NP_114129.1
TAF3	XM_011519741.2	c.530A>G	p.Lys177Arg	missense_variant	3/7		XP_011518043.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF3	ENST00000344293.6	c.533A>G	p.Lys178Arg	missense_variant	3/7	1	NM_031923.4	ENSP00000340271.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2024

The c.533A>G (p.K178R) alteration is located in exon 3 (coding exon 3) of the TAF3 gene. This alteration results from a A to G substitution at nucleotide position 533, causing the lysine (K) at amino acid position 178 to be replaced by an arginine (R). 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	0.12
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.13
Sift	Benign	0.080	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.65
MutPred		0.20		Loss of ubiquitination at K178 (P = 4e-04);
MVP		0.27
MPC		0.70
ClinPred		0.77	D
GERP RS		5.6
Varity_R		0.17
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-8006006;