chr9-130681605-TCGCCGCCGCCGCCGCCGC-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_021619.3(PRDM12):c.1059_1076delCGCCGCCGCCGCCGCCGC(p.Ala354_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 0.0104 in 955,234 control chromosomes in the GnomAD database, including 53 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 (★★).

Frequency

Genomes: 𝑓 0.0078 ( 7 hom., cov: 0)

Exomes 𝑓: 0.011 ( 46 hom. )

Consequence

PRDM12
NM_021619.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

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-TCGCCGCCGCCGCCGCCGC-T is Benign according to our data. Variant chr9-130681605-TCGCCGCCGCCGCCGCCGC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 475807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00778 (1104/141912) while in subpopulation NFE AF = 0.012 (773/64610). AF 95% confidence interval is 0.0113. There are 7 homozygotes in GnomAd4. There are 521 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM12	NM_021619.3 link	c.1059_1076delCGCCGCCGCCGCCGCCGC	p.Ala354_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.1059_1076delCGCCGCCGCCGCCGCCGC	p.Ala354_Ala359del	disruptive_inframe_deletion	Exon 5 of 5	1	NM_021619.3	ENSP00000253008.2		Q9H4Q4
PRDM12	ENST00000676323.1 link	c.906+153_906+170delCGCCGCCGCCGCCGCCGC		intron_variant	Intron 5 of 5			ENSP00000502471.1		A0A6Q8PH01

Frequencies

GnomAD3 genomes

AF:

0.00777

AC:

1103

AN:

141872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00311

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00588

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.000426

Gnomad SAS

AF:

0.00238

Gnomad FIN

AF:

0.00435

Gnomad MID

AF:

0.0103

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.00674

GnomAD2 exomes

AF:

0.0625

AC:

AN:

AF XY:

0.125

show subpopulations

Gnomad NFE exome

AF:

0.0625

GnomAD4 exome

AF:

0.0108

AC:

8787

AN:

813322

Hom.:

AF XY:

0.0109

AC XY:

4126

AN XY:

377244

show subpopulations

African (AFR)

AF:

0.00304

AC:

AN:

14820

American (AMR)

AF:

0.00549

AC:

AN:

1274

Ashkenazi Jewish (ASJ)

AF:

0.0178

AC:

AN:

5224

East Asian (EAS)

AF:

0.000253

AC:

AN:

3952

South Asian (SAS)

AF:

0.00228

AC:

AN:

16206

European-Finnish (FIN)

AF:

0.00140

AC:

AN:

1430

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

1600

European-Non Finnish (NFE)

AF:

0.0112

AC:

8298

AN:

742058

Other (OTH)

AF:

0.0107

AC:

287

AN:

26758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.594

Heterozygous variant carriers

287

574

861

1148

1435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.00778

AC:

1104

AN:

141912

Hom.:

Cov.:

AF XY:

0.00758

AC XY:

521

AN XY:

68750

show subpopulations

African (AFR)

AF:

0.00313

AC:

123

AN:

39292

American (AMR)

AF:

0.00587

AC:

AN:

14472

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

3350

East Asian (EAS)

AF:

0.000427

AC:

AN:

4680

South Asian (SAS)

AF:

0.00261

AC:

AN:

4604

European-Finnish (FIN)

AF:

0.00435

AC:

AN:

7818

Middle Eastern (MID)

AF:

0.00752

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.0120

AC:

773

AN:

64610

Other (OTH)

AF:

0.00669

AC:

AN:

1944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

104

157

209

261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00318

Hom.:

347

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PRDM12: BS1, BS2 -

Nov 02, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=191/9

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over