Variant 9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The ENST00000253008.3(PRDM12):c.1059_1076del(p.Ala354_Ala359del) variant causes a 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. 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
ENST00000253008.3 inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely 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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in ENST00000253008.3

BP6

Variant 9-130681605-TCGCCGCCGCCGCCGCCGC-T is Benign according to our data. Variant chr9-130681605-TCGCCGCCGCCGCCGCCGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 475807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-130681605-TCGCCGCCGCCGCCGCCGC-T is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM12	NM_021619.3 linkuse as main transcript	c.1059_1076del	p.Ala354_Ala359del	inframe_deletion	5/5	ENST00000253008.3	NP_067632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM12	ENST00000253008.3 linkuse as main transcript	c.1059_1076del	p.Ala354_Ala359del	inframe_deletion	5/5	1	NM_021619.3	ENSP00000253008	P1
PRDM12	ENST00000676323.1 linkuse as main transcript	c.906+153_906+170del		intron_variant				ENSP00000502471

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

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:

0.0108

AC:

8787

AN:

813322

Hom.:

AF XY:

0.0109

AC XY:

4126

AN XY:

377244

show subpopulations

Gnomad4 AFR exome

AF:

0.00304

Gnomad4 AMR exome

AF:

0.00549

Gnomad4 ASJ exome

AF:

0.0178

Gnomad4 EAS exome

AF:

0.000253

Gnomad4 SAS exome

AF:

0.00228

Gnomad4 FIN exome

AF:

0.00140

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.00778

AC:

1104

AN:

141912

Hom.:

Cov.:

AF XY:

0.00758

AC XY:

521

AN XY:

68750

show subpopulations

Gnomad4 AFR

AF:

0.00313

Gnomad4 AMR

AF:

0.00587

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.000427

Gnomad4 SAS

AF:

0.00261

Gnomad4 FIN

AF:

0.00435

Gnomad4 NFE

AF:

0.0120

Gnomad4 OTH

AF:

0.00669

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

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 02, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	PRDM12: BS1, BS2 -

Congenital insensitivity to pain-hypohidrosis syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

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