NM_001040424.3:c.-9-5871G>C

Variant names:

• chr21-41866243-C-G
• rs2839398
• NM_001040424.3:c.-9-5871G>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.-9-5871G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,290 control chromosomes in the GnomAD database, including 1,463 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 0.13 (1463 hom., cov: 34)
• Consequence: PRDM15 NM_001040424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 10 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 (EAS) allele frequency at 95% confidence interval = 0.315 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.-9-5871G>C		intron	N/A	NP_001035514.2	P57071-7
	PRDM15	NM_022115.7		c.-282+1057G>C		intron	N/A	NP_071398.5
	PRDM15	NM_001282934.2		c.-9-5871G>C		intron	N/A	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.-9-5871G>C		intron	N/A	ENSP00000381556.2	P57071-7
	PRDM15	ENST00000269844.5	TSL:1	c.-282+1057G>C		intron	N/A	ENSP00000269844.4	A0AB56DNF6
	PRDM15	ENST00000422911.6	TSL:1	c.-9-5871G>C		intron	N/A	ENSP00000408592.2	P57071-2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19506 AN: 152172 Hom.: 1460 Cov.: 34

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0912

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.128 AC: 19527 AN: 152290 Hom.: 1463 Cov.: 34 AF XY: 0.131 AC XY: 9769 AN XY: 74468

African (AFR) AF: 0.164 AC: 6826 AN: 41546

American (AMR) AF: 0.136 AC: 2076 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3472

East Asian (EAS) AF: 0.328 AC: 1701 AN: 5186

South Asian (SAS) AF: 0.134 AC: 649 AN: 4830

European-Finnish (FIN) AF: 0.134 AC: 1422 AN: 10604

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0912 AC: 6203 AN: 68028

Other (OTH) AF: 0.131 AC: 277 AN: 2116

Alfa AF: 0.0421 Hom.: 36

Bravo AF: 0.130

Asia WGS AF: 0.230 AC: 800 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	5.1
DANN	Benign	0.55
PhyloP100		-0.10
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: rs2839398; hg19: chr21-43286352;