10-7965597-T-C

Variant names:

• chr10-7965597-T-C
• rs1244229
• NM_031923.4:c.2087T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031923.4(TAF3):​c.2087T>C​(p.Val696Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,588,220 control chromosomes in the GnomAD database, including 398,234 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (35776 hom., cov: 26)
  • Exomes 𝑓: 0.71 (362458 hom.)
• Consequence: TAF3 NM_031923.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• Publications: 23 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.45388E-7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF3	NM_031923.4	MANE Select	c.2087T>C	p.Val696Ala	missense	Exon 3 of 7	NP_114129.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF3	ENST00000344293.6	TSL:1 MANE Select	c.2087T>C	p.Val696Ala	missense	Exon 3 of 7	ENSP00000340271.5
	TAF3	ENST00000687522.1		c.2084T>C	p.Val695Ala	missense	Exon 3 of 7	ENSP00000508875.1
	TAF3	ENST00000686593.1		n.*1650T>C		non_coding_transcript_exon	Exon 3 of 4	ENSP00000509355.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 103293 AN: 147826 Hom.: 35753 Cov.: 26

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.727

GnomAD2 exomes AF: 0.726 AC: 170323 AN: 234536 AF XY: 0.726

Gnomad AFR exome AF: 0.591

Gnomad AMR exome AF: 0.830

Gnomad ASJ exome AF: 0.800

Gnomad EAS exome AF: 0.715

Gnomad FIN exome AF: 0.727

Gnomad NFE exome AF: 0.706

Gnomad OTH exome AF: 0.736

GnomAD4 exome AF: 0.708 AC: 1020292 AN: 1440286 Hom.: 362458 Cov.: 53 AF XY: 0.710 AC XY: 508506 AN XY: 715940

African (AFR) AF: 0.595 AC: 19151 AN: 32180

American (AMR) AF: 0.824 AC: 33525 AN: 40694

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 20514 AN: 25434

East Asian (EAS) AF: 0.760 AC: 29690 AN: 39056

South Asian (SAS) AF: 0.751 AC: 60801 AN: 80942

European-Finnish (FIN) AF: 0.724 AC: 38234 AN: 52792

Middle Eastern (MID) AF: 0.775 AC: 4393 AN: 5666

European-Non Finnish (NFE) AF: 0.699 AC: 772275 AN: 1104150

Other (OTH) AF: 0.703 AC: 41709 AN: 59372

GnomAD4 genome AF: 0.699 AC: 103352 AN: 147934 Hom.: 35776 Cov.: 26 AF XY: 0.705 AC XY: 50802 AN XY: 72026

African (AFR) AF: 0.614 AC: 24272 AN: 39506

American (AMR) AF: 0.782 AC: 11668 AN: 14912

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2794 AN: 3450

East Asian (EAS) AF: 0.725 AC: 3627 AN: 5000

South Asian (SAS) AF: 0.746 AC: 3500 AN: 4690

European-Finnish (FIN) AF: 0.747 AC: 7503 AN: 10040

Middle Eastern (MID) AF: 0.797 AC: 231 AN: 290

European-Non Finnish (NFE) AF: 0.709 AC: 47593 AN: 67090

Other (OTH) AF: 0.725 AC: 1490 AN: 2056

Alfa AF: 0.705 Hom.: 78922

Bravo AF: 0.686

TwinsUK AF: 0.689 AC: 2554

ALSPAC AF: 0.687 AC: 2649

ESP6500AA AF: 0.601 AC: 2218

ESP6500EA AF: 0.712 AC: 5817

ExAC AF: 0.722 AC: 87263

Asia WGS AF: 0.672 AC: 2340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	19
DANN	Benign	0.84
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	6.5e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.19
Sift	Benign	0.19	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.047
MPC		0.24
ClinPred		0.0091	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.036
gMVP		0.018
Mutation Taster		=100/0	polymorphism (auto)

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: rs1244229; hg19: chr10-8007560; COSMIC: COSV60207032;