10-7964498-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_031923.4(TAF3):c.988A>T(p.Ile330Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,613,440 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (34 hom.)
• Consequence: TAF3 NM_031923.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.181

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023827255).
• BP6: Variant 10-7964498-A-T is Benign according to our data. Variant chr10-7964498-A-T is described in ClinVar as [Benign]. Clinvar id is 785305.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1905/152276) while in subpopulation AFR AF= 0.0435 (1808/41544). AF 95% confidence interval is 0.0418. There are 40 homozygotes in gnomad4. There are 919 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1899 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF3	NM_031923.4	c.988A>T	p.Ile330Phe	missense_variant	3/7	ENST00000344293.6
TAF3	XM_011519741.2	c.985A>T	p.Ile329Phe	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF3	ENST00000344293.6	c.988A>T	p.Ile330Phe	missense_variant	3/7	1	NM_031923.4	P4

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1899 AN: 152158 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00286 AC: 703 AN: 245654 Hom.: 19 AF XY: 0.00228 AC XY: 304 AN XY: 133594

Gnomad AFR exome AF: 0.0411

Gnomad AMR exome AF: 0.00190

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000632

Gnomad OTH exome AF: 0.000668

GnomAD4 exome AF: 0.00115 AC: 1678 AN: 1461164 Hom.: 34 Cov.: 30 AF XY: 0.000964 AC XY: 701 AN XY: 726896

Gnomad4 AFR exome AF: 0.0419

Gnomad4 AMR exome AF: 0.00220

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000279

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.0125 AC: 1905 AN: 152276 Hom.: 40 Cov.: 32 AF XY: 0.0123 AC XY: 919 AN XY: 74474

Gnomad4 AFR AF: 0.0435

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.000909 Hom.: 2

Bravo AF: 0.0140

ESP6500AA AF: 0.0401 AC: 150

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00342 AC: 413

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

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	5.5
Dann	Benign	0.83
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.022
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.041	D
Polyphen		0.090	B
Vest4		0.13
MVP		0.15
MPC		0.36
ClinPred		0.0032	T
GERP RS		-3.3
Varity_R		0.12
gMVP		0.036

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: rs61731331; hg19: chr10-8006461;