chr6-106099497-C-G

Variant names:

• chr6-106099497-C-G
• rs811925
• NM_001198.4:c.609C>G

Variant summary

Our verdict is Benign. The variant received -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 (★).

• 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
• Publications: 48 publications found

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]

ATG5 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 25

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM1	NM_001198.4	MANE Select	c.609C>G	p.Asp203Glu	missense	Exon 4 of 7	NP_001189.2	O75626-1
	PRDM1	NM_182907.3		c.207C>G	p.Asp69Glu	missense	Exon 2 of 5	NP_878911.1	O75626-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM1	ENST00000369096.9	TSL:1 MANE Select	c.609C>G	p.Asp203Glu	missense	Exon 4 of 7	ENSP00000358092.4	O75626-1
	PRDM1	ENST00000369091.6	TSL:1	c.501C>G	p.Asp167Glu	missense	Exon 4 of 7	ENSP00000358087.2	O75626-2
	PRDM1	ENST00000369089.3	TSL:1	c.207C>G	p.Asp69Glu	missense	Exon 2 of 5	ENSP00000358085.3	O75626-3

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

GnomAD2 exomes AF: 0.162 AC: 40749 AN: 251394 AF XY: 0.165

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 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

African (AFR) AF: 0.155 AC: 5172 AN: 33474

American (AMR) AF: 0.140 AC: 6272 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3563 AN: 26134

East Asian (EAS) AF: 0.0211 AC: 837 AN: 39674

South Asian (SAS) AF: 0.186 AC: 16047 AN: 86256

European-Finnish (FIN) AF: 0.231 AC: 12351 AN: 53418

Middle Eastern (MID) AF: 0.158 AC: 910 AN: 5768

European-Non Finnish (NFE) AF: 0.171 AC: 190638 AN: 1111904

Other (OTH) AF: 0.164 AC: 9918 AN: 60394

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

African (AFR) AF: 0.159 AC: 6598 AN: 41518

American (AMR) AF: 0.142 AC: 2174 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 536 AN: 3468

East Asian (EAS) AF: 0.0197 AC: 102 AN: 5188

South Asian (SAS) AF: 0.192 AC: 923 AN: 4812

European-Finnish (FIN) AF: 0.239 AC: 2528 AN: 10558

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11727 AN: 68010

Other (OTH) AF: 0.164 AC: 346 AN: 2112

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.21	N
REVEL	Uncertain	0.42
Sift	Benign	0.71	T
Sift4G	Benign	1.0	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
Mutation Taster		=53/47	polymorphism (auto)

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

Other links and lift over

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