9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGC

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.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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A354A) has been classified 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: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-TCGCCGCCGCCGCCGC-T is Benign according to our data. Variant chr9-130681605-TCGCCGCCGCCGCCGC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId 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

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
PRDM12	ENST00000676323.1 link	c.906+156_906+170delCGCCGCCGCCGCCGC		intron_variant	Intron 5 of 5			ENSP00000502471.1

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

GnomAD2 exomes

AF:

0.00

AC:

AN:

AF XY:

0.00

Gnomad NFE exome

AF:

0.00

GnomAD4 exome

AF:

0.00748

AC:

6080

AN:

813332

Hom.:

183

AF XY:

0.00736

AC XY:

2776

AN XY:

377252

show subpopulations

African (AFR)

AF:

0.00250

AC:

AN:

14820

American (AMR)

AF:

0.0157

AC:

AN:

1274

Ashkenazi Jewish (ASJ)

AF:

0.00900

AC:

AN:

5224

East Asian (EAS)

AF:

0.222

AC:

880

AN:

3958

South Asian (SAS)

AF:

0.0618

AC:

1001

AN:

16208

European-Finnish (FIN)

AF:

0.000699

AC:

AN:

1430

Middle Eastern (MID)

AF:

0.00750

AC:

AN:

1600

European-Non Finnish (NFE)

AF:

0.00464

AC:

3444

AN:

742054

Other (OTH)

AF:

0.0238

AC:

638

AN:

26764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.587

Heterozygous variant carriers

210

420

631

841

1051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

240

480

720

960

1200

<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:

0.0156

AC:

2213

AN:

141906

Hom.:

152

Cov.:

AF XY:

0.0178

AC XY:

1224

AN XY:

68750

show subpopulations

African (AFR)

AF:

0.00270

AC:

106

AN:

39292

American (AMR)

AF:

0.0283

AC:

409

AN:

14470

Ashkenazi Jewish (ASJ)

AF:

0.0134

AC:

AN:

3350

East Asian (EAS)

AF:

0.224

AC:

1048

AN:

4678

South Asian (SAS)

AF:

0.0639

AC:

294

AN:

4602

European-Finnish (FIN)

AF:

0.00422

AC:

AN:

7820

Middle Eastern (MID)

AF:

0.0150

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.00382

AC:

247

AN:

64608

Other (OTH)

AF:

0.0134

AC:

AN:

1944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

184

277

369

461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00159

Hom.:

347

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

PhyloP100

1.3

Mutation Taster

=192/8

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over