17-35822556-G-A

Position:

• chr17-35822556-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139215.3(TAF15):​c.291-84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,271,484 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (78 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (56 hom.)
• Consequence: TAF15 NM_139215.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.889

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]

ENSG00000270894 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-35822556-G-A is Benign according to our data. Variant chr17-35822556-G-A is described in ClinVar as [Benign]. Clinvar id is 1220985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF15	NM_139215.3	c.291-84G>A		intron_variant		ENST00000605844.6	NP_631961.1
TAF15	NM_003487.4	c.282-84G>A		intron_variant			NP_003478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF15	ENST00000605844.6	c.291-84G>A		intron_variant		1	NM_139215.3	ENSP00000474096.1

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2602 AN: 152076 Hom.: 78 Cov.: 32

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00211 AC: 2363 AN: 1119290 Hom.: 56 AF XY: 0.00186 AC XY: 1050 AN XY: 565964

Gnomad4 AFR exome AF: 0.0643

Gnomad4 AMR exome AF: 0.00435

Gnomad4 ASJ exome AF: 0.00188

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000217

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000280

Gnomad4 OTH exome AF: 0.00447

GnomAD4 genome AF: 0.0172 AC: 2615 AN: 152194 Hom.: 78 Cov.: 32 AF XY: 0.0170 AC XY: 1268 AN XY: 74418

Gnomad4 AFR AF: 0.0588

Gnomad4 AMR AF: 0.00700

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0139 Hom.: 6

Bravo AF: 0.0197

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.55
DANN	Benign	0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs4251745; hg19: chr17-34149560;