chr10-7964556-G-C

Variant names:

• chr10-7964556-G-C
• rs17366712
• NM_031923.4:c.1046G>C

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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 0.032 (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
• Publications: 13 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=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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4896 AD gene.

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.1046G>C	p.Ser349Thr	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.1046G>C	p.Ser349Thr	missense	Exon 3 of 7	ENSP00000340271.5
	TAF3	ENST00000687522.1		c.1043G>C	p.Ser348Thr	missense	Exon 3 of 7	ENSP00000508875.1
	TAF3	ENST00000686593.1		n.*609G>C		non_coding_transcript_exon	Exon 3 of 4	ENSP00000509355.1

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

GnomAD2 exomes AF: 0.0366 AC: 9089 AN: 248252 AF XY: 0.0363

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 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

African (AFR) AF: 0.00729 AC: 244 AN: 33470

American (AMR) AF: 0.0409 AC: 1828 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 649 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39676

South Asian (SAS) AF: 0.0278 AC: 2397 AN: 86244

European-Finnish (FIN) AF: 0.0517 AC: 2761 AN: 53384

Middle Eastern (MID) AF: 0.0165 AC: 95 AN: 5768

European-Non Finnish (NFE) AF: 0.0495 AC: 55066 AN: 1111898

Other (OTH) AF: 0.0383 AC: 2315 AN: 60390

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

African (AFR) AF: 0.00857 AC: 356 AN: 41520

American (AMR) AF: 0.0334 AC: 510 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3468

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5170

South Asian (SAS) AF: 0.0216 AC: 104 AN: 4822

European-Finnish (FIN) AF: 0.0575 AC: 608 AN: 10576

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0461 AC: 3133 AN: 67984

Other (OTH) AF: 0.0303 AC: 64 AN: 2110

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 v4.9

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
PhyloP100		3.8
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
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: rs17366712; hg19: chr10-8006519; COSMIC: COSV60206620;