rs1244229

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-7965597-T-A
• chr10-7965597-T-C
• chr10-7965597-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031923.4(TAF3):​c.2087T>A​(p.Val696Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000203 in 148,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 0.000020 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000016 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032011002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF3	NM_031923.4	c.2087T>A	p.Val696Glu	missense_variant	Exon 3 of 7	ENST00000344293.6	NP_114129.1
TAF3	XM_011519741.2	c.2084T>A	p.Val695Glu	missense_variant	Exon 3 of 7		XP_011518043.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF3	ENST00000344293.6	c.2087T>A	p.Val696Glu	missense_variant	Exon 3 of 7	1	NM_031923.4	ENSP00000340271.5

Frequencies

GnomAD3 genomes AF: 0.0000203 AC: 3 AN: 147914 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000160 AC: 23 AN: 1441342 Hom.: 0 Cov.: 53 AF XY: 0.0000209 AC XY: 15 AN XY: 716482

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000620 AC: 2 AN: 32244

American (AMR) AF: 0.0000245 AC: 1 AN: 40786

Ashkenazi Jewish (ASJ) AF: 0.0000393 AC: 1 AN: 25450

East Asian (EAS) AF: 0.00 AC: 0 AN: 39108

South Asian (SAS) AF: 0.0000616 AC: 5 AN: 81118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.0000118 AC: 13 AN: 1104684

Other (OTH) AF: 0.0000168 AC: 1 AN: 59434

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000203 AC: 3 AN: 148022 Hom.: 0 Cov.: 26 AF XY: 0.0000139 AC XY: 1 AN XY: 72078

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000506 AC: 2 AN: 39548

American (AMR) AF: 0.00 AC: 0 AN: 14916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5000

South Asian (SAS) AF: 0.00 AC: 0 AN: 4694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67118

Other (OTH) AF: 0.00 AC: 0 AN: 2056

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 78922

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.59
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.63
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.076	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.59	N
PhyloP100		2.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.76	N
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.17		Loss of MoRF binding (P = 0.0248);
MVP		0.068
MPC		0.32
ClinPred		0.37	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.017
Mutation Taster		=99/1	polymorphism

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;