rs11244096

Variant names:

• chr9-130675957-G-A
• rs11244096
• NM_021619.3:c.571-2572G>A

Variant summary

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

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]

PRDM12 Gene-Disease associations (from GenCC):

• congenital insensitivity to pain-hypohidrosis syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• hereditary sensory and autonomic neuropathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina

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 = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM12	NM_021619.3	c.571-2572G>A		intron_variant	Intron 3 of 4	ENST00000253008.3	NP_067632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM12	ENST00000253008.3	c.571-2572G>A		intron_variant	Intron 3 of 4	1	NM_021619.3	ENSP00000253008.2
PRDM12	ENST00000676323.1	c.571-2572G>A		intron_variant	Intron 3 of 5			ENSP00000502471.1

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

African (AFR) AF: 0.0555 AC: 2306 AN: 41532

American (AMR) AF: 0.330 AC: 5041 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 853 AN: 3468

East Asian (EAS) AF: 0.433 AC: 2227 AN: 5148

South Asian (SAS) AF: 0.280 AC: 1349 AN: 4826

European-Finnish (FIN) AF: 0.323 AC: 3407 AN: 10544

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.281 AC: 19076 AN: 67960

Other (OTH) AF: 0.276 AC: 581 AN: 2106

Alfa AF: 0.267 Hom.: 3865

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
PhyloP100		-2.7
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: rs11244096; hg19: chr9-133551344;