NM_001040424.3:c.2652+2595T>C

Variant names:

• chr21-41807559-A-G
• rs7279297
• NM_001040424.3:c.2652+2595T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040424.3(PRDM15):​c.2652+2595T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,550 control chromosomes in the GnomAD database, including 10,124 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 (10124 hom., cov: 31)
• Consequence: PRDM15 NM_001040424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• Publications: 15 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 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.2652+2595T>C		intron	N/A	NP_001035514.2
	PRDM15	NM_022115.7		c.2850+2595T>C		intron	N/A	NP_071398.5
	PRDM15	NM_001282934.2		c.2712+2595T>C		intron	N/A	NP_001269863.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM15	ENST00000398548.6	TSL:1 MANE Select	c.2652+2595T>C		intron	N/A	ENSP00000381556.2
	PRDM15	ENST00000269844.5	TSL:1	c.2850+2595T>C		intron	N/A	ENSP00000269844.4
	PRDM15	ENST00000422911.6	TSL:1	c.2712+2595T>C		intron	N/A	ENSP00000408592.2

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53445 AN: 151434 Hom.: 10112 Cov.: 31

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.353 AC: 53493 AN: 151550 Hom.: 10124 Cov.: 31 AF XY: 0.356 AC XY: 26340 AN XY: 74026

African (AFR) AF: 0.467 AC: 19255 AN: 41250

American (AMR) AF: 0.289 AC: 4391 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3472

East Asian (EAS) AF: 0.535 AC: 2742 AN: 5126

South Asian (SAS) AF: 0.517 AC: 2466 AN: 4772

European-Finnish (FIN) AF: 0.295 AC: 3099 AN: 10518

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19372 AN: 67908

Other (OTH) AF: 0.366 AC: 768 AN: 2098

Alfa AF: 0.324 Hom.: 13639

Bravo AF: 0.356

Asia WGS AF: 0.476 AC: 1655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.40
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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: rs7279297; hg19: chr21-43227915;