9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGC

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:4

Conservation

PhyloP100: 1.33

Publications

1 publications found

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 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

PRDM12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 475809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021619.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM12	NM_021619.3	MANE Select	c.1068_1076delCGCCGCCGC	p.Ala357_Ala359del	disruptive_inframe_deletion	Exon 5 of 5	NP_067632.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM12	ENST00000253008.3	TSL:1 MANE Select	c.1068_1076delCGCCGCCGC	p.Ala357_Ala359del	disruptive_inframe_deletion	Exon 5 of 5	ENSP00000253008.2
	PRDM12	ENST00000676323.1		c.906+162_906+170delCGCCGCCGC		intron	N/A	ENSP00000502471.1

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

GnomAD2 exomes

AF:

0.0625

AC:

AN:

AF XY:

0.125

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

African (AFR)

AF:

0.0263

AC:

389

AN:

14818

American (AMR)

AF:

0.0306

AC:

AN:

1274

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

523

AN:

5224

East Asian (EAS)

AF:

0.00531

AC:

AN:

3958

South Asian (SAS)

AF:

0.0170

AC:

275

AN:

16210

European-Finnish (FIN)

AF:

0.0119

AC:

AN:

1428

Middle Eastern (MID)

AF:

0.0575

AC:

AN:

1600

European-Non Finnish (NFE)

AF:

0.0679

AC:

50359

AN:

742024

Other (OTH)

AF:

0.0552

AC:

1478

AN:

26764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.573

Heterozygous variant carriers

2233

4467

6700

8934

11167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2580

5160

7740

10320

12900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0482

AC:

6836

AN:

141884

Hom.:

211

Cov.:

AF XY:

0.0460

AC XY:

3164

AN XY:

68736

show subpopulations

African (AFR)

AF:

0.0259

AC:

1016

AN:

39286

American (AMR)

AF:

0.0532

AC:

770

AN:

14468

Ashkenazi Jewish (ASJ)

AF:

0.0918

AC:

307

AN:

3346

East Asian (EAS)

AF:

0.00748

AC:

AN:

4680

South Asian (SAS)

AF:

0.0161

AC:

AN:

4604

European-Finnish (FIN)

AF:

0.0488

AC:

382

AN:

7820

Middle Eastern (MID)

AF:

0.0414

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.0638

AC:

4122

AN:

64592

Other (OTH)

AF:

0.0591

AC:

115

AN:

1946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

308

616

925

1233

1541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0216

Hom.:

347

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

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 v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=197/3

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over