rs11244096

Positions:

• chr9-130675957-G-A

Variant summary

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

The NM_021619.3(PRDM12):​c.571-2572G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,064 control chromosomes in the GnomAD database, including 5,126 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 0.23 (5126 hom., cov: 32)
• Consequence: PRDM12 NM_021619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

Genes affected

PRDM12 (HGNC:13997): (PR/SET domain 12) This gene encodes a transcriptional regulator of sensory neuronal specification that plays a critical role in pain perception. The encoded protein contains an N-terminal PRDI-BF1 and RIZ homology (PR) domain, a SET domain, and three C-terminal C2H2 zinc finger DNA-binding domains. Naturally occurring mutations in this gene are associated with congenital insensitivity to pain (CIP), and hereditary sensory and autonomic neuropathies (HSAN's) affecting peripheral sensory and autonomic neurons. Deregulation of this gene is associated with solid cancers and hematological malignancies including chronic myeloid leukaemia. [provided by RefSeq, Mar 2017]

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 (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM12	NM_021619.3	c.571-2572G>A		intron_variant		ENST00000253008.3	NP_067632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM12	ENST00000253008.3	c.571-2572G>A		intron_variant		1	NM_021619.3	ENSP00000253008	P1
PRDM12	ENST00000676323.1	c.571-2572G>A		intron_variant				ENSP00000502471

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35231 AN: 151946 Hom.: 5129 Cov.: 32

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.232 AC: 35222 AN: 152064 Hom.: 5126 Cov.: 32 AF XY: 0.237 AC XY: 17590 AN XY: 74292

Gnomad4 AFR AF: 0.0555

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.276

Alfa AF: 0.267 Hom.: 2764

Bravo AF: 0.229

Asia WGS AF: 0.313 AC: 1084 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	0.079
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs11244096; hg19: chr9-133551344;