17-35864402-T-C

Variant names:

• chr17-35864402-T-C
• rs2291299
• NM_152781.4:c.510+95A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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]

TAF15 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152781.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR9	NM_152781.4	MANE Select	c.510+95A>G		intron	N/A	NP_689994.2
	HEATR9	NM_001321395.2		c.390+95A>G		intron	N/A	NP_001308324.1
	HEATR9	NR_135630.2		n.659+95A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR9	ENST00000604834.6	TSL:1 MANE Select	c.510+95A>G		intron	N/A	ENSP00000473941.1
	HEATR9	ENST00000603323.5	TSL:1	n.510+95A>G		intron	N/A	ENSP00000474391.1
	TAF15	ENST00000603967.1	TSL:3	c.*134T>C		3_prime_UTR	Exon 2 of 2	ENSP00000474047.1

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

African (AFR) AF: 0.449 AC: 14111 AN: 31430

American (AMR) AF: 0.266 AC: 11761 AN: 44248

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 4925 AN: 25430

East Asian (EAS) AF: 0.351 AC: 13687 AN: 39038

South Asian (SAS) AF: 0.274 AC: 23128 AN: 84330

European-Finnish (FIN) AF: 0.175 AC: 9342 AN: 53308

Middle Eastern (MID) AF: 0.191 AC: 1056 AN: 5520

European-Non Finnish (NFE) AF: 0.178 AC: 184721 AN: 1035382

Other (OTH) AF: 0.209 AC: 11976 AN: 57402

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

African (AFR) AF: 0.438 AC: 18152 AN: 41408

American (AMR) AF: 0.236 AC: 3612 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 628 AN: 3466

East Asian (EAS) AF: 0.344 AC: 1776 AN: 5160

South Asian (SAS) AF: 0.293 AC: 1413 AN: 4818

European-Finnish (FIN) AF: 0.178 AC: 1878 AN: 10564

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12154 AN: 67950

Other (OTH) AF: 0.236 AC: 499 AN: 2112

Alfa AF: 0.210 Hom.: 10544

Bravo AF: 0.277

Asia WGS AF: 0.310 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.70
DANN	Benign	0.55
PhyloP100		-1.2

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

Other links and lift over

dbSNP: rs2291299; hg19: chr17-34191406;