NM_031923.4:c.706A>C

Variant names:

• chr10-7964216-A-C
• rs376032844
• NM_031923.4:c.706A>C

Variant summary

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

The NM_031923.4(TAF3):​c.706A>C​(p.Ser236Arg) variant causes a missense change involving the alteration of a 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S236G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF3 NM_031923.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.15
• Publications: 0 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: 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=0.14070106).

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.706A>C	p.Ser236Arg	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.706A>C	p.Ser236Arg	missense	Exon 3 of 7	ENSP00000340271.5	Q5VWG9
	TAF3	ENST00000687522.1		c.703A>C	p.Ser235Arg	missense	Exon 3 of 7	ENSP00000508875.1	A0A8I5KR98
	TAF3	ENST00000686593.1		n.*269A>C		non_coding_transcript_exon	Exon 3 of 4	ENSP00000509355.1	A0A8I5QJF0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.0035
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		8.2
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.081
Sift	Benign	0.13	T
Sift4G	Benign	0.082	T
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.13		Loss of glycosylation at S236 (P = 0.0069)
MVP		0.12
MPC		0.35
ClinPred		0.46	T
GERP RS		5.7
Varity_R		0.071
gMVP		0.25
Mutation Taster		=78/22	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: rs376032844; hg19: chr10-8006179;