11-93737212-A-G

Variant names:

• chr11-93737212-A-G
• NM_024116.4:c.487T>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.487T>C​(p.Tyr163His) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF1D NM_024116.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.38
• Publications: 0 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=0.16664705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1D	NM_024116.4	c.487T>C	p.Tyr163His	missense_variant	Exon 4 of 6	ENST00000448108.7	NP_077021.1
TAF1D	NR_146090.2	n.688T>C		non_coding_transcript_exon_variant	Exon 4 of 14
TAF1D	NR_146091.2	n.688T>C		non_coding_transcript_exon_variant	Exon 4 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1D	ENST00000448108.7	c.487T>C	p.Tyr163His	missense_variant	Exon 4 of 6	5	NM_024116.4	ENSP00000410409.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.487T>C (p.Y163H) alteration is located in exon 4 (coding exon 3) of the TAF1D gene. This alteration results from a T to C substitution at nucleotide position 487, causing the tyrosine (Y) at amino acid position 163 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	-0.066
Eigen_PC	Benign	0.066
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.17
Sift	Benign	0.30	T
Sift4G	Benign	0.17	T
Polyphen		0.41	B
Vest4		0.42
MutPred		0.52		Gain of disorder (P = 0.0359);
MVP		0.24
MPC		0.58
ClinPred		0.91	D
GERP RS		4.4
Varity_R		0.12
gMVP		0.28
Mutation Taster		=93/7	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

hg19: chr11-93470378;