11-93738179-C-A

Variant names:

• chr11-93738179-C-A
• rs758705344
• NM_024116.4:c.389G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024116.4(TAF1D):​c.389G>T​(p.Gly130Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G130E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TAF1D NM_024116.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 2 publications found

Genes affected

TAF1D (HGNC:28759): (TATA-box binding protein associated factor, RNA polymerase I subunit D) TAF1D is a member of the SL1 complex, which includes TBP (MIM 600075) and TAF1A (MIM 604903), TAF1B (MIM 604904), and TAF1C (MIM 604905), and plays a role in RNA polymerase I transcription (Wang et al., 2004 [PubMed 15520167]; Gorski et al., 2007 [PubMed 17318177]).[supplied by OMIM, Jun 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37091038).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024116.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1D	NM_024116.4	MANE Select	c.389G>T	p.Gly130Val	missense	Exon 3 of 6	NP_077021.1	Q9H5J8
	TAF1D	NR_146090.2		n.590G>T		non_coding_transcript_exon	Exon 3 of 14
	TAF1D	NR_146091.2		n.590G>T		non_coding_transcript_exon	Exon 3 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1D	ENST00000448108.7	TSL:5 MANE Select	c.389G>T	p.Gly130Val	missense	Exon 3 of 6	ENSP00000410409.2	Q9H5J8
	TAF1D	ENST00000526015.5	TSL:1	n.389G>T		non_coding_transcript_exon	Exon 3 of 14	ENSP00000435087.1	Q9H5J8
	TAF1D	ENST00000883225.1		c.389G>T	p.Gly130Val	missense	Exon 3 of 6	ENSP00000553284.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426032 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 708682

African (AFR) AF: 0.00 AC: 0 AN: 30968

American (AMR) AF: 0.00 AC: 0 AN: 34094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24340

East Asian (EAS) AF: 0.00 AC: 0 AN: 38958

South Asian (SAS) AF: 0.00 AC: 0 AN: 78362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5578

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102212

Other (OTH) AF: 0.0000170 AC: 1 AN: 58732

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	0.16
Eigen_PC	Benign	0.00059
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.1
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.28		Loss of disorder (P = 0.0641)
MVP		0.37
MPC		0.57
ClinPred		0.98	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.59
gMVP		0.23
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs758705344; hg19: chr11-93471345;