17-35820594-G-A

Position:

• chr17-35820594-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_139215.3(TAF15):​c.290+157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 151,926 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.011 (16 hom., cov: 32)
• Consequence: TAF15 NM_139215.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.589

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-35820594-G-A is Benign according to our data. Variant chr17-35820594-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1181146.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0105 (1600/151926) while in subpopulation NFE AF= 0.0186 (1262/67928). AF 95% confidence interval is 0.0177. There are 16 homozygotes in gnomad4. There are 732 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1600 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF15	NM_139215.3	c.290+157G>A		intron_variant		ENST00000605844.6	NP_631961.1
TAF15	NM_003487.4	c.281+157G>A		intron_variant			NP_003478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF15	ENST00000605844.6	c.290+157G>A		intron_variant		1	NM_139215.3	ENSP00000474096.1

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1603 AN: 151808 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.00609

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.00575

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0105 AC: 1600 AN: 151926 Hom.: 16 Cov.: 32 AF XY: 0.00986 AC XY: 732 AN XY: 74242

Gnomad4 AFR AF: 0.00256

Gnomad4 AMR AF: 0.00524

Gnomad4 ASJ AF: 0.00289

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.00609

Gnomad4 NFE AF: 0.0186

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.0180 Hom.: 3

Bravo AF: 0.00921

Asia WGS AF: 0.00376 AC: 13 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.79
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs4251738; hg19: chr17-34147598;