Variant 9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC 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.1071_1076dupCGCCGC(p.Ala358_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 0.043 ( 171 hom., cov: 0)

Exomes 𝑓: 0.033 ( 292 hom. )

Consequence

PRDM12
NM_021619.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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-TCGCCGC is Benign according to our data. Variant chr9-130681605-T-TCGCCGC is described in ClinVar as [Benign]. Clinvar id is 475812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM12	NM_021619.3 link	c.1071_1076dupCGCCGC	p.Ala358_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.1071_1076dupCGCCGC	p.Ala358_Ala359dup	disruptive_inframe_insertion	Exon 5 of 5	1	NM_021619.3	ENSP00000253008.2		Q9H4Q4
PRDM12	ENST00000676323.1 link	c.906+165_906+170dupCGCCGC		intron_variant	Intron 5 of 5			ENSP00000502471.1		A0A6Q8PH01

Frequencies

GnomAD3 genomes

AF:

0.0427

AC:

6052

AN:

141834

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0691

Gnomad AMI

AF:

0.00571

Gnomad AMR

AF:

0.0318

Gnomad ASJ

AF:

0.0128

Gnomad EAS

AF:

0.0309

Gnomad SAS

AF:

0.0232

Gnomad FIN

AF:

0.0199

Gnomad MID

AF:

0.0137

Gnomad NFE

AF:

0.0364

Gnomad OTH

AF:

0.0383

GnomAD4 exome

AF:

0.0327

AC:

26517

AN:

811666

Hom.:

292

Cov.:

AF XY:

0.0325

AC XY:

12245

AN XY:

376500

show subpopulations

Gnomad4 AFR exome

AF:

0.0666

Gnomad4 AMR exome

AF:

0.0134

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.0261

Gnomad4 SAS exome

AF:

0.0227

Gnomad4 FIN exome

AF:

0.00490

Gnomad4 NFE exome

AF:

0.0326

Gnomad4 OTH exome

AF:

0.0303

GnomAD4 genome

AF:

0.0427

AC:

6055

AN:

141872

Hom.:

171

Cov.:

AF XY:

0.0410

AC XY:

2818

AN XY:

68726

show subpopulations

Gnomad4 AFR

AF:

0.0691

Gnomad4 AMR

AF:

0.0317

Gnomad4 ASJ

AF:

0.0128

Gnomad4 EAS

AF:

0.0306

Gnomad4 SAS

AF:

0.0233

Gnomad4 FIN

AF:

0.0199

Gnomad4 NFE

AF:

0.0364

Gnomad4 OTH

AF:

0.0385

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital insensitivity to pain-hypohidrosis syndrome

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Oct 06, 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