rs752427775

Variant names:

• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-T
• rs752427775
• NM_021619.3:c.1053_1076delCGCCGCCGCCGCCGCCGCCGCCGC

Your query was ambiguous. Multiple possible variants found:

• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-T
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC
• chr9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_021619.3(PRDM12):​c.1053_1076delCGCCGCCGCCGCCGCCGCCGCCGC​(p.Ala352_Ala359del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000398 in 955,256 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00011 (1 hom., cov: 0)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: PRDM12 NM_021619.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_021619.3

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM12	NM_021619.3	c.1053_1076delCGCCGCCGCCGCCGCCGCCGCCGC	p.Ala352_Ala359del	disruptive_inframe_deletion	Exon 5 of 5	ENST00000253008.3	NP_067632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM12	ENST00000253008.3	c.1053_1076delCGCCGCCGCCGCCGCCGCCGCCGC	p.Ala352_Ala359del	disruptive_inframe_deletion	Exon 5 of 5	1	NM_021619.3	ENSP00000253008.2
PRDM12	ENST00000676323.1	c.906+147_906+170delCGCCGCCGCCGCCGCCGCCGCCGC		intron_variant	Intron 5 of 5			ENSP00000502471.1

Frequencies

GnomAD3 genomes AF: 0.000106 AC: 15 AN: 141876 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000277

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000283 AC: 23 AN: 813340 Hom.: 0 AF XY: 0.0000212 AC XY: 8 AN XY: 377256

African (AFR) AF: 0.000270 AC: 4 AN: 14820

American (AMR) AF: 0.00 AC: 0 AN: 1274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5224

East Asian (EAS) AF: 0.00 AC: 0 AN: 3958

South Asian (SAS) AF: 0.0000617 AC: 1 AN: 16210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1600

European-Non Finnish (NFE) AF: 0.0000243 AC: 18 AN: 742060

Other (OTH) AF: 0.00 AC: 0 AN: 26764

GnomAD4 genome AF: 0.000106 AC: 15 AN: 141916 Hom.: 1 Cov.: 0 AF XY: 0.0000727 AC XY: 5 AN XY: 68754

African (AFR) AF: 0.000280 AC: 11 AN: 39292

American (AMR) AF: 0.000276 AC: 4 AN: 14472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3350

East Asian (EAS) AF: 0.00 AC: 0 AN: 4680

South Asian (SAS) AF: 0.00 AC: 0 AN: 4604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64610

Other (OTH) AF: 0.00 AC: 0 AN: 1946

Alfa AF: 0.00 Hom.: 347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=191/9	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs752427775; hg19: chr9-133556992;