11-62782713-G-A

Position:

• chr11-62782713-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006473.4(TAF6L):​c.848G>A​(p.Ser283Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TAF6L NM_006473.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.37

Genes affected

TAF6L (HGNC:17305): (TATA-box binding protein associated factor 6 like) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes a protein that is a component of the PCAF histone acetylase complex and structurally similar to one of the histone-like TAFs, TAF6. The PCAF histone acetylase complex, which is composed of more than 20 polypeptides some of which are TAFs, is required for myogenic transcription and differentiation. [provided by RefSeq, Jul 2008]

TMEM223 (HGNC:28464): (transmembrane protein 223) Predicted to be involved in nervous system development. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07820231).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF6L	NM_006473.4	c.848G>A	p.Ser283Asn	missense_variant	9/11	ENST00000294168.8	NP_006464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF6L	ENST00000294168.8	c.848G>A	p.Ser283Asn	missense_variant	9/11	1	NM_006473.4	ENSP00000294168	P1
TMEM223	ENST00000528367.1	c.315-8048C>T		intron_variant		2		ENSP00000431804
TMEM223	ENST00000527073.1	n.66-8048C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460024 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726318

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.848G>A (p.S283N) alteration is located in exon 9 (coding exon 8) of the TAF6L gene. This alteration results from a G to A substitution at nucleotide position 848, causing the serine (S) at amino acid position 283 to be replaced by an asparagine (N). 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	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.80
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.089
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.95	L
MutationTaster	Benign	0.82	N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.064
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.16
MutPred		0.37		Loss of glycosylation at S283 (P = 0.0183);
MVP		0.23
MPC		0.60
ClinPred		0.68	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.060
gMVP		0.089

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2084239425; hg19: chr11-62550185;