10-7964581-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_031923.4(TAF3):c.1071C>T(p.Ile357=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00936 in 1,614,012 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0096 (92 hom.)
• Consequence: TAF3 NM_031923.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.547

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-7964581-C-T is Benign according to our data. Variant chr10-7964581-C-T is described in ClinVar as [Benign]. Clinvar id is 778458.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.547 with no splicing effect.
• BS2: High AC in GnomAd at 1104 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF3	NM_031923.4	c.1071C>T	p.Ile357=	synonymous_variant	3/7	ENST00000344293.6
TAF3	XM_011519741.2	c.1068C>T	p.Ile356=	synonymous_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF3	ENST00000344293.6	c.1071C>T	p.Ile357=	synonymous_variant	3/7	1	NM_031923.4	P4

Frequencies

GnomAD3 genomes AF: 0.00726 AC: 1104 AN: 152068 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00750 AC: 1866 AN: 248788 Hom.: 15 AF XY: 0.00779 AC XY: 1052 AN XY: 135016

Gnomad AFR exome AF: 0.00149

Gnomad AMR exome AF: 0.00406

Gnomad ASJ exome AF: 0.00339

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00301

Gnomad FIN exome AF: 0.0167

Gnomad NFE exome AF: 0.0104

Gnomad OTH exome AF: 0.00745

GnomAD4 exome AF: 0.00958 AC: 14009 AN: 1461826 Hom.: 92 Cov.: 31 AF XY: 0.00936 AC XY: 6807 AN XY: 727206

Gnomad4 AFR exome AF: 0.00185

Gnomad4 AMR exome AF: 0.00452

Gnomad4 ASJ exome AF: 0.00356

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00319

Gnomad4 FIN exome AF: 0.0186

Gnomad4 NFE exome AF: 0.0106

Gnomad4 OTH exome AF: 0.00853

GnomAD4 genome AF: 0.00724 AC: 1102 AN: 152186 Hom.: 9 Cov.: 32 AF XY: 0.00722 AC XY: 537 AN XY: 74396

Gnomad4 AFR AF: 0.00161

Gnomad4 AMR AF: 0.00543

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.0166

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00829 Hom.: 2

Bravo AF: 0.00613

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.24
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs149754469; hg19: chr10-8006544;