rs811925

Positions:

• chr6-106099497-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001198.4(PRDM1):​c.609C>G​(p.Asp203Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,910 control chromosomes in the GnomAD database, including 23,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (2220 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21525 hom.)
• Consequence: PRDM1 NM_001198.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 1.77

Genes affected

PRDM1 (HGNC:9346): (PR/SET domain 1) This gene encodes a protein that acts as a repressor of beta-interferon gene expression. The protein binds specifically to the PRDI (positive regulatory domain I element) of the beta-IFN gene promoter. Transcription of this gene increases upon virus induction. Two alternatively spliced transcript variants that encode different isoforms have been reported. [provided by RefSeq, Jul 2008]

ATG5 (HGNC:589): (autophagy related 5) The protein encoded by this gene, in combination with autophagy protein 12, functions as an E1-like activating enzyme in a ubiquitin-like conjugating system. The encoded protein is involved in several cellular processes, including autophagic vesicle formation, mitochondrial quality control after oxidative damage, negative regulation of the innate antiviral immune response, lymphocyte development and proliferation, MHC II antigen presentation, adipocyte differentiation, and apoptosis. Several transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018483102).
• BP6: Variant 6-106099497-C-G is Benign according to our data. Variant chr6-106099497-C-G is described in ClinVar as [Benign]. Clinvar id is 135076.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM1	NM_001198.4	c.609C>G	p.Asp203Glu	missense_variant	4/7	ENST00000369096.9	NP_001189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM1	ENST00000369096.9	c.609C>G	p.Asp203Glu	missense_variant	4/7	1	NM_001198.4	ENSP00000358092	A1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25171 AN: 152046 Hom.: 2223 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0194

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.165

GnomAD3 exomes AF: 0.162 AC: 40749 AN: 251394 Hom.: 3530 AF XY: 0.165 AC XY: 22454 AN XY: 135880

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.135

Gnomad EAS exome AF: 0.0184

Gnomad SAS exome AF: 0.186

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.168 AC: 245708 AN: 1461746 Hom.: 21525 Cov.: 33 AF XY: 0.169 AC XY: 122681 AN XY: 727178

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.0211

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.165 AC: 25176 AN: 152164 Hom.: 2220 Cov.: 32 AF XY: 0.169 AC XY: 12536 AN XY: 74370

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0197

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.164

Alfa AF: 0.165 Hom.: 1617

Bravo AF: 0.157

TwinsUK AF: 0.174 AC: 646

ALSPAC AF: 0.164 AC: 631

ESP6500AA AF: 0.163 AC: 717

ESP6500EA AF: 0.169 AC: 1457

ExAC AF: 0.165 AC: 20045

Asia WGS AF: 0.119 AC: 412 AN: 3478

EpiCase AF: 0.177

EpiControl AF: 0.177

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2020

This variant is associated with the following publications: (PMID: 21085059) -

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.82
DEOGEN2	Benign	0.29	.;T;.;.;.
Eigen	Benign	-0.090
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.63	T;T;T;T;T
MetaRNN	Benign	0.0018	T;T;T;T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.4	.;M;.;.;.
MutationTaster	Benign	0.00083	P;P;P
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.21	N;N;.;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.71	T;T;.;T;T
Sift4G	Benign	1.0	T;T;.;T;T
Polyphen		0.57	.;P;.;.;.
Vest4		0.12
MutPred		0.60		.;Loss of sheet (P = 0.1907);.;.;.;
MPC		0.38
ClinPred		0.036	T
GERP RS		5.9
Varity_R		0.50
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs811925; hg19: chr6-106547372; COSMIC: COSV64844571; COSMIC: COSV64844571;