rs17366712

Positions:

• chr10-7964556-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_031923.4(TAF3):​c.1046G>C​(p.Ser349Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0435 in 1,613,814 control chromosomes in the GnomAD database, including 1,730 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.032 (105 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1625 hom.)
• Consequence: TAF3 NM_031923.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026902258).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0322 (4896/152144) while in subpopulation NFE AF= 0.0461 (3133/67984). AF 95% confidence interval is 0.0447. There are 105 homozygotes in gnomad4. There are 2371 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4896 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF3	NM_031923.4	c.1046G>C	p.Ser349Thr	missense_variant	3/7	ENST00000344293.6	NP_114129.1
TAF3	XM_011519741.2	c.1043G>C	p.Ser348Thr	missense_variant	3/7		XP_011518043.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF3	ENST00000344293.6	c.1046G>C	p.Ser349Thr	missense_variant	3/7	1	NM_031923.4	ENSP00000340271	P4

Frequencies

GnomAD3 genomes AF: 0.0322 AC: 4897 AN: 152026 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.00860

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0461

Gnomad OTH AF: 0.0307

GnomAD3 exomes AF: 0.0366 AC: 9089 AN: 248252 Hom.: 204 AF XY: 0.0363 AC XY: 4887 AN XY: 134766

Gnomad AFR exome AF: 0.00813

Gnomad AMR exome AF: 0.0422

Gnomad ASJ exome AF: 0.0251

Gnomad EAS exome AF: 0.000224

Gnomad SAS exome AF: 0.0276

Gnomad FIN exome AF: 0.0555

Gnomad NFE exome AF: 0.0446

Gnomad OTH exome AF: 0.0327

GnomAD4 exome AF: 0.0447 AC: 65360 AN: 1461670 Hom.: 1625 Cov.: 31 AF XY: 0.0439 AC XY: 31888 AN XY: 727110

Gnomad4 AFR exome AF: 0.00729

Gnomad4 AMR exome AF: 0.0409

Gnomad4 ASJ exome AF: 0.0248

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0278

Gnomad4 FIN exome AF: 0.0517

Gnomad4 NFE exome AF: 0.0495

Gnomad4 OTH exome AF: 0.0383

GnomAD4 genome AF: 0.0322 AC: 4896 AN: 152144 Hom.: 105 Cov.: 32 AF XY: 0.0319 AC XY: 2371 AN XY: 74370

Gnomad4 AFR AF: 0.00857

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0216

Gnomad4 FIN AF: 0.0575

Gnomad4 NFE AF: 0.0461

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0376 Hom.: 87

Bravo AF: 0.0296

TwinsUK AF: 0.0529 AC: 196

ALSPAC AF: 0.0529 AC: 204

ESP6500AA AF: 0.00778 AC: 29

ESP6500EA AF: 0.0449 AC: 368

ExAC AF: 0.0353 AC: 4261

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.84
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	0.95	D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.13
Sift	Benign	0.037	D
Sift4G	Benign	0.57	T
Polyphen		0.18	B
Vest4		0.050
MPC		0.47
ClinPred		0.020	T
GERP RS		3.5
Varity_R		0.037
gMVP		0.17

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

LitVar

Other links and lift over

dbSNP: rs17366712; hg19: chr10-8006519; COSMIC: COSV60206620;