6-106105382-G-C

Variant names:

• chr6-106105382-G-C
• rs144524449
• NM_001198.4:c.1222G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001198.4(PRDM1):​c.1222G>C​(p.Ala408Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000554 in 1,613,926 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.00062 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (2 hom.)
• Consequence: PRDM1 NM_001198.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.568

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011618227).
• BS2: High AC in GnomAd4 at 95 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM1	NM_001198.4	c.1222G>C	p.Ala408Pro	missense_variant	Exon 5 of 7	ENST00000369096.9	NP_001189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM1	ENST00000369096.9	c.1222G>C	p.Ala408Pro	missense_variant	Exon 5 of 7	1	NM_001198.4	ENSP00000358092.4

Frequencies

GnomAD3 genomes AF: 0.000625 AC: 95 AN: 151968 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.000573 AC: 144 AN: 251242 AF XY: 0.000618

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000678

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000547 AC: 799 AN: 1461842 Hom.: 2 Cov.: 32 AF XY: 0.000554 AC XY: 403 AN XY: 727224

Gnomad4 AFR exome AF: 0.000239 AC: 8 AN: 33480

Gnomad4 AMR exome AF: 0.000425 AC: 19 AN: 44724

Gnomad4 ASJ exome AF: 0.00149 AC: 39 AN: 26134

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.000672 AC: 58 AN: 86258

Gnomad4 FIN exome AF: 0.0000375 AC: 2 AN: 53386

Gnomad4 NFE exome AF: 0.000538 AC: 598 AN: 1112000

Gnomad4 Remaining exome AF: 0.000745 AC: 45 AN: 60392

GnomAD4 genome AF: 0.000625 AC: 95 AN: 152084 Hom.: 1 Cov.: 32 AF XY: 0.000754 AC XY: 56 AN XY: 74318

Gnomad4 AFR AF: 0.0000965 AC: 0.0000964506 AN: 0.0000964506

Gnomad4 AMR AF: 0.00144 AC: 0.00143866 AN: 0.00143866

Gnomad4 ASJ AF: 0.00115 AC: 0.0011534 AN: 0.0011534

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00208 AC: 0.0020842 AN: 0.0020842

Gnomad4 FIN AF: 0.0000945 AC: 0.0000945001 AN: 0.0000945001

Gnomad4 NFE AF: 0.000662 AC: 0.000661882 AN: 0.000661882

Gnomad4 OTH AF: 0.00190 AC: 0.00189753 AN: 0.00189753

Alfa AF: 0.000690 Hom.: 0

Bravo AF: 0.000638

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.000626 AC: 76

EpiCase AF: 0.00131

EpiControl AF: 0.00119

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.18	.;T;.;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.012	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	.;L;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.68	N;N;.;N
REVEL	Benign	0.039
Sift	Benign	0.36	T;T;.;T
Sift4G	Benign	0.54	T;T;.;T
Polyphen		0.0	.;B;.;.
Vest4		0.13
MVP		0.12
MPC		0.50
ClinPred		0.0080	T
GERP RS		2.4
Varity_R		0.091
gMVP		0.45
Mutation Taster		=98/2	polymorphism

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: rs144524449; hg19: chr6-106553257; COSMIC: COSV104426916;