10-7964835-A-C

Variant names:

• chr10-7964835-A-C
• rs4747647
• NM_031923.4:c.1325A>C

Variant summary

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

The NM_031923.4(TAF3):​c.1325A>C​(p.Asn442Thr) 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. 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. N442Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TAF3 NM_031923.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 29 publications found

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]

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=0.044888467).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031923.4. 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
	TAF3	NM_031923.4	MANE Select	c.1325A>C	p.Asn442Thr	missense	Exon 3 of 7	NP_114129.1	Q5VWG9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF3	ENST00000344293.6	TSL:1 MANE Select	c.1325A>C	p.Asn442Thr	missense	Exon 3 of 7	ENSP00000340271.5	Q5VWG9
	TAF3	ENST00000687522.1		c.1322A>C	p.Asn441Thr	missense	Exon 3 of 7	ENSP00000508875.1	A0A8I5KR98
	TAF3	ENST00000686593.1		n.*888A>C		non_coding_transcript_exon	Exon 3 of 4	ENSP00000509355.1	A0A8I5QJF0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 77

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.33
DANN	Benign	0.95
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.16
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.045
Sift	Benign	0.21	T
Sift4G	Benign	0.26	T
Polyphen		0.0020	B
Vest4		0.095
MutPred		0.083		Gain of phosphorylation at N442 (P = 0.032)
MVP		0.20
MPC		0.27
ClinPred		0.11	T
GERP RS		1.7
Varity_R		0.022
gMVP		0.15
Mutation Taster		=95/5	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: rs4747647; hg19: chr10-8006798;