Variant 9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGC 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.1074_1076dupCGC(p.Ala359dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 11866 hom., cov: 0)

Exomes 𝑓: 0.29 ( 19887 hom. )

Consequence

PRDM12
NM_021619.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0910

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-T-TCGC is Benign according to our data. Variant chr9-130681605-T-TCGC is described in ClinVar as [Benign]. Clinvar id is 475813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM12	NM_021619.3 link	c.1074_1076dupCGC	p.Ala359dup	disruptive_inframe_insertion	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.1074_1076dupCGC	p.Ala359dup	disruptive_inframe_insertion	Exon 5 of 5	1	NM_021619.3	ENSP00000253008.2		Q9H4Q4
PRDM12	ENST00000676323.1 link	c.906+168_906+170dupCGC		intron_variant	Intron 5 of 5			ENSP00000502471.1		A0A6Q8PH01

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

56728

AN:

141750

Hom.:

11863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.470

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.608

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.295

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.389

GnomAD4 exome

AF:

0.291

AC:

234747

AN:

807512

Hom.:

19887

Cov.:

AF XY:

0.290

AC XY:

108501

AN XY:

374572

show subpopulations

Gnomad4 AFR exome

AF:

0.416

Gnomad4 AMR exome

AF:

0.338

Gnomad4 ASJ exome

AF:

0.230

Gnomad4 EAS exome

AF:

0.402

Gnomad4 SAS exome

AF:

0.378

Gnomad4 FIN exome

AF:

0.0575

Gnomad4 NFE exome

AF:

0.286

Gnomad4 OTH exome

AF:

0.310

GnomAD4 genome

AF:

0.400

AC:

56740

AN:

141788

Hom.:

11866

Cov.:

AF XY:

0.405

AC XY:

27848

AN XY:

68684

show subpopulations

Gnomad4 AFR

AF:

0.470

Gnomad4 AMR

AF:

0.480

Gnomad4 ASJ

AF:

0.268

Gnomad4 EAS

AF:

0.608

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.392

Gnomad4 NFE

AF:

0.330

Gnomad4 OTH

AF:

0.392

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Congenital insensitivity to pain-hypohidrosis syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PRDM12-related disorder

Benign:1

Mar 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

not provided

Benign:1

Aug 20, 2019

GeneDx

Significance: 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