Variant chr9-130681605-TCGCCGCCGC-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.1068_1076delCGCCGCCGC(p.Ala357_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 0.0628 in 955,184 control chromosomes in the GnomAD database, including 1,801 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 211 hom., cov: 0)

Exomes 𝑓: 0.065 ( 1590 hom. )

Consequence

PRDM12
NM_021619.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

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-TCGCCGCCGC-T is Benign according to our data. Variant chr9-130681605-TCGCCGCCGC-T is described in ClinVar as [Benign]. Clinvar id is 475809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-130681605-TCGCCGCCGC-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM12	NM_021619.3 link	c.1068_1076delCGCCGCCGC	p.Ala357_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.1068_1076delCGCCGCCGC	p.Ala357_Ala359del	disruptive_inframe_deletion	Exon 5 of 5	1	NM_021619.3	ENSP00000253008.2		Q9H4Q4
PRDM12	ENST00000676323.1 link	c.906+162_906+170delCGCCGCCGC		intron_variant	Intron 5 of 5			ENSP00000502471.1		A0A6Q8PH01

Frequencies

GnomAD3 genomes

AF:

0.0482

AC:

6836

AN:

141844

Hom.:

211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0258

Gnomad AMI

AF:

0.00457

Gnomad AMR

AF:

0.0533

Gnomad ASJ

AF:

0.0918

Gnomad EAS

AF:

0.00746

Gnomad SAS

AF:

0.0162

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.0377

Gnomad NFE

AF:

0.0638

Gnomad OTH

AF:

0.0595

GnomAD3 exomes

AF:

0.0625

AC:

AN:

Hom.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

Gnomad NFE exome

AF:

0.0625

GnomAD4 exome

AF:

0.0654

AC:

53193

AN:

813300

Hom.:

1590

AF XY:

0.0652

AC XY:

24605

AN XY:

377240

show subpopulations

Gnomad4 AFR exome

AF:

0.0263

Gnomad4 AMR exome

AF:

0.0306

Gnomad4 ASJ exome

AF:

0.100

Gnomad4 EAS exome

AF:

0.00531

Gnomad4 SAS exome

AF:

0.0170

Gnomad4 FIN exome

AF:

0.0119

Gnomad4 NFE exome

AF:

0.0679

Gnomad4 OTH exome

AF:

0.0552

GnomAD4 genome

AF:

0.0482

AC:

6836

AN:

141884

Hom.:

211

Cov.:

AF XY:

0.0460

AC XY:

3164

AN XY:

68736

show subpopulations

Gnomad4 AFR

AF:

0.0259

Gnomad4 AMR

AF:

0.0532

Gnomad4 ASJ

AF:

0.0918

Gnomad4 EAS

AF:

0.00748

Gnomad4 SAS

AF:

0.0161

Gnomad4 FIN

AF:

0.0488

Gnomad4 NFE

AF:

0.0638

Gnomad4 OTH

AF:

0.0591

ClinVar

Significance: 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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Jul 23, 2019

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Aug 18, 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