NM_024116.4:c.421G>C

Variant names:

• chr11-93738147-C-G
• rs761554639
• NM_024116.4:c.421G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024116.4(TAF1D):​c.421G>C​(p.Glu141Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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. E141K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF1D NM_024116.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08272532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1D	NM_024116.4	c.421G>C	p.Glu141Gln	missense_variant	Exon 3 of 6	ENST00000448108.7	NP_077021.1
TAF1D	NR_146090.2	n.622G>C		non_coding_transcript_exon_variant	Exon 3 of 14
TAF1D	NR_146091.2	n.622G>C		non_coding_transcript_exon_variant	Exon 3 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1D	ENST00000448108.7	c.421G>C	p.Glu141Gln	missense_variant	Exon 3 of 6	5	NM_024116.4	ENSP00000410409.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.94
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.047
Sift	Benign	0.25	T
Sift4G	Benign	0.51	T
Polyphen		0.67	P
Vest4		0.15
MutPred		0.20		Loss of solvent accessibility (P = 0.0721);
MVP		0.31
MPC		0.18
ClinPred		0.18	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.031
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs761554639; hg19: chr11-93471313;