Variant chr9-130681605-TCGCCGCCGCCGCCGC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_021619.3(PRDM12):c.1062_1076delCGCCGCCGCCGCCGC(p.Ala355_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 0.00868 in 955,238 control chromosomes in the GnomAD database, including 335 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 152 hom., cov: 0)

Exomes 𝑓: 0.0075 ( 183 hom. )

Consequence

PRDM12
NM_021619.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.33

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_021619.3

BP6

Variant 9-130681605-TCGCCGCCGCCGCCGC-T is Benign according to our data. Variant chr9-130681605-TCGCCGCCGCCGCCGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 475808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM12	NM_021619.3 link	c.1062_1076delCGCCGCCGCCGCCGC	p.Ala355_Ala359del	disruptive_inframe_deletion	Exon 5 of 5	ENST00000253008.3	NP_067632.2	Q9H4Q4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM12	ENST00000253008.3 link	c.1062_1076delCGCCGCCGCCGCCGC	p.Ala355_Ala359del	disruptive_inframe_deletion	Exon 5 of 5	1	NM_021619.3	ENSP00000253008.2		Q9H4Q4
PRDM12	ENST00000676323.1 link	c.906+156_906+170delCGCCGCCGCCGCCGC		intron_variant	Intron 5 of 5			ENSP00000502471.1		A0A6Q8PH01

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2214

AN:

141868

Hom.:

153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00114

Gnomad AMR

AF:

0.0282

Gnomad ASJ

AF:

0.0134

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.0634

Gnomad FIN

AF:

0.00422

Gnomad MID

AF:

0.0137

Gnomad NFE

AF:

0.00382

Gnomad OTH

AF:

0.0129

GnomAD4 exome

AF:

0.00748

AC:

6080

AN:

813332

Hom.:

183

AF XY:

0.00736

AC XY:

2776

AN XY:

377252

show subpopulations

Gnomad4 AFR exome

AF:

0.00250

Gnomad4 AMR exome

AF:

0.0157

Gnomad4 ASJ exome

AF:

0.00900

Gnomad4 EAS exome

AF:

0.222

Gnomad4 SAS exome

AF:

0.0618

Gnomad4 FIN exome

AF:

0.000699

Gnomad4 NFE exome

AF:

0.00464

Gnomad4 OTH exome

AF:

0.0238

GnomAD4 genome

AF:

0.0156

AC:

2213

AN:

141906

Hom.:

152

Cov.:

AF XY:

0.0178

AC XY:

1224

AN XY:

68750

show subpopulations

Gnomad4 AFR

AF:

0.00270

Gnomad4 AMR

AF:

0.0283

Gnomad4 ASJ

AF:

0.0134

Gnomad4 EAS

AF:

0.224

Gnomad4 SAS

AF:

0.0639

Gnomad4 FIN

AF:

0.00422

Gnomad4 NFE

AF:

0.00382

Gnomad4 OTH

AF:

0.0134

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital insensitivity to pain-hypohidrosis syndrome

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PRDM12-related disorder

Benign:1

Jul 12, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Nov 26, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over