21-41800831-G-A

Variant names:

• chr21-41800831-G-A
• rs2236693
• NM_001040424.3:c.*409C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

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 = 0.467 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040424.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM15	NM_001040424.3	MANE Select	c.*409C>T		3_prime_UTR	Exon 24 of 24	NP_001035514.2	P57071-7
	PRDM15	NM_022115.7		c.*409C>T		3_prime_UTR	Exon 31 of 31	NP_071398.5
	PRDM15	NM_001282934.2		c.*409C>T		3_prime_UTR	Exon 25 of 25	NP_001269863.2	P57071-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM15	ENST00000398548.6	TSL:1 MANE Select	c.*409C>T		3_prime_UTR	Exon 24 of 24	ENSP00000381556.2	P57071-7
	PRDM15	ENST00000422911.6	TSL:1	c.*409C>T		3_prime_UTR	Exon 25 of 25	ENSP00000408592.2	P57071-2
	PRDM15	ENST00000441787.5	TSL:1	n.*2286C>T		non_coding_transcript_exon	Exon 24 of 24	ENSP00000387958.1	Q4W8S1

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

African (AFR) AF: 0.438 AC: 247 AN: 564

American (AMR) AF: 0.244 AC: 144 AN: 590

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 117 AN: 490

East Asian (EAS) AF: 0.267 AC: 142 AN: 532

South Asian (SAS) AF: 0.314 AC: 66 AN: 210

European-Finnish (FIN) AF: 0.254 AC: 142 AN: 560

Middle Eastern (MID) AF: 0.333 AC: 24 AN: 72

European-Non Finnish (NFE) AF: 0.289 AC: 2801 AN: 9684

Other (OTH) AF: 0.302 AC: 260 AN: 862

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

African (AFR) AF: 0.473 AC: 19604 AN: 41484

American (AMR) AF: 0.293 AC: 4476 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3470

East Asian (EAS) AF: 0.291 AC: 1505 AN: 5178

South Asian (SAS) AF: 0.390 AC: 1877 AN: 4818

European-Finnish (FIN) AF: 0.272 AC: 2873 AN: 10574

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20835 AN: 67984

Other (OTH) AF: 0.334 AC: 705 AN: 2110

Alfa AF: 0.318 Hom.: 13299

Bravo AF: 0.357

Asia WGS AF: 0.307 AC: 1070 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	1.2
DANN	Benign	0.29
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2236693; hg19: chr21-43220991;