rs2236693

chr21-41800831-G-Achr21-41800831-G-C

Variant summary

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

The NM_001040424.3(PRDM15):c.*409C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 165,690 control chromosomes in the GnomAD database, including 10,436 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 0.35 (9821 hom., cov: 33)
  • Exomes 𝑓: 0.29 (615 hom.)
• Consequence: PRDM15 NM_001040424.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

Genes affected

PRDM15 (HGNC:13999): (PR/SET domain 15) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and promoter-specific chromatin binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II; regulation of signal transduction; and regulation of stem cell division. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM15	NM_001040424.3	c.*409C>T		3_prime_UTR_variant	24/24	ENST00000398548.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM15	ENST00000398548.6	c.*409C>T		3_prime_UTR_variant	24/24	1	NM_001040424.3	P2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53074 AN: 152008 Hom.: 9803 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.291 AC: 3943 AN: 13564 Hom.: 615 Cov.: 0 AF XY: 0.291 AC XY: 1963 AN XY: 6756

Gnomad4 AFR exome AF: 0.438

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.349 AC: 53131 AN: 152126 Hom.: 9821 Cov.: 33 AF XY: 0.346 AC XY: 25754 AN XY: 74364

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.334

Alfa AF: 0.314 Hom.: 10212

Bravo AF: 0.357

Asia WGS AF: 0.307 AC: 1070 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	1.2
Dann	Benign	0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2236693; hg19: chr21-43220991;