11-93738318-A-C

Variant names:

• chr11-93738318-A-C
• NM_024116.4:c.250T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024116.4(TAF1D):​c.250T>G​(p.Phe84Val) 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. 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: 2.16

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34788346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1D	NM_024116.4	c.250T>G	p.Phe84Val	missense_variant	Exon 3 of 6	ENST00000448108.7	NP_077021.1
TAF1D	NR_146090.2	n.451T>G		non_coding_transcript_exon_variant	Exon 3 of 14
TAF1D	NR_146091.2	n.451T>G		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.250T>G	p.Phe84Val	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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.250T>G (p.F84V) alteration is located in exon 3 (coding exon 2) of the TAF1D gene. This alteration results from a T to G substitution at nucleotide position 250, causing the phenylalanine (F) at amino acid position 84 to be replaced by a valine (V). 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.0035	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Benign	0.97
Eigen	Benign	-0.099
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.95	P
Vest4		0.54
MutPred		0.26		Gain of methylation at K89 (P = 0.1433);
MVP		0.42
MPC		0.31
ClinPred		0.92	D
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.27
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-93471484;