17-35864402-T-C

Position:

• chr17-35864402-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152781.4(HEATR9):​c.510+95A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,528,044 control chromosomes in the GnomAD database, including 36,340 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6366 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29974 hom.)
• Consequence: HEATR9 NM_152781.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

HEATR9 (HGNC:26548): (HEAT repeat containing 9) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEATR9	NM_152781.4	c.510+95A>G		intron_variant		ENST00000604834.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEATR9	ENST00000604834.6	c.510+95A>G		intron_variant		1	NM_152781.4	P2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40277 AN: 151840 Hom.: 6333 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.200 AC: 274707 AN: 1376088 Hom.: 29974 Cov.: 22 AF XY: 0.200 AC XY: 137771 AN XY: 687386

Gnomad4 AFR exome AF: 0.449

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.351

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.266 AC: 40371 AN: 151956 Hom.: 6366 Cov.: 32 AF XY: 0.266 AC XY: 19760 AN XY: 74300

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.236

Alfa AF: 0.194 Hom.: 5517

Bravo AF: 0.277

Asia WGS AF: 0.310 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.70
DANN	Benign	0.55

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: rs2291299; hg19: chr17-34191406;