17-35809574-C-T

Position:

• chr17-35809574-C-T

Variant summary

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

The NM_139215.3(TAF15):​c.5C>T​(p.Ser2Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF15 NM_139215.3 missense, splice_region
• Scores: Splicing: ADA: 0.9804
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.16

Genes affected

TAF15 (HGNC:11547): (TATA-box binding protein associated factor 15) This gene encodes a member of the TET family of RNA-binding proteins. The encoded protein plays a role in RNA polymerase II gene transcription as a component of a distinct subset of multi-subunit transcription initiation factor TFIID complexes. Translocations involving this gene play a role in acute leukemia and extraskeletal myxoid chondrosarcoma, and mutations in this gene may play a role in amyotrophic lateral sclerosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF15	NM_139215.3	c.5C>T	p.Ser2Leu	missense_variant, splice_region_variant	1/16	ENST00000605844.6	NP_631961.1
TAF15	NM_003487.4	c.5C>T	p.Ser2Leu	missense_variant, splice_region_variant	1/16		NP_003478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF15	ENST00000605844.6	c.5C>T	p.Ser2Leu	missense_variant, splice_region_variant	1/16	1	NM_139215.3	ENSP00000474096.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Apr 29, 2024

The c.5C>T (p.S2L) alteration is located in exon 1 (coding exon 1) of the TAF15 gene. This alteration results from a C to T substitution at nucleotide position 5, causing the serine (S) at amino acid position 2 to be replaced by a leucine (L). 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	0.32
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Pathogenic	0.58	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	0.55	N;.;N
PrimateAI	Uncertain	0.73	T
Sift4G	Uncertain	0.048	D;D;T
Polyphen		0.0050	B;.;B
Vest4		0.65
MutPred		0.13		Loss of phosphorylation at S2 (P = 0.0034);Loss of phosphorylation at S2 (P = 0.0034);Loss of phosphorylation at S2 (P = 0.0034);
MVP		0.88
ClinPred		0.95	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.24
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Pathogenic	0.81
SpliceAI score (max)		0.050		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: rs1299588637; hg19: chr17-34136578;