rs150632206

Variant names:

• chr4-80203145-C-T
• rs150632206
• NM_001099403.2:c.1683C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001099403.2(PRDM8):​c.1683C>T​(p.Ser561Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,554,360 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (66 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (92 hom.)
• Consequence: PRDM8 NM_001099403.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.708
• Publications: 2 publications found

Genes affected

PRDM8 (HGNC:13993): (PR/SET domain 8) This gene encodes a protein that belongs to a conserved family of histone methyltransferases that predominantly act as negative regulators of transcription. The encoded protein contains an N-terminal Su(var)3-9, Enhancer-of-zeste, and Trithorax (SET) domain and a double zinc-finger domain. Knockout of this gene in mouse results in mistargeting by neurons of the dorsal telencephalon, abnormal itch-like behavior, and impaired differentiation of rod bipolar cells. In humans, the protein has been shown to interact with the phosphatase laforin and the ubiquitin ligase malin, which regulate glycogen construction in the cytoplasm. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

PRDM8 Gene-Disease associations (from GenCC):

• early-onset Lafora body disease

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 4-80203145-C-T is Benign according to our data. Variant chr4-80203145-C-T is described in ClinVar as Benign. ClinVar VariationId is 475672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.708 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099403.2. 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
	PRDM8	NM_001099403.2	MANE Select	c.1683C>T	p.Ser561Ser	synonymous	Exon 4 of 4	NP_001092873.1	Q9NQV8-1
	PRDM8	NM_020226.4		c.1683C>T	p.Ser561Ser	synonymous	Exon 10 of 10	NP_064611.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM8	ENST00000415738.3	TSL:1 MANE Select	c.1683C>T	p.Ser561Ser	synonymous	Exon 4 of 4	ENSP00000406998.2	Q9NQV8-1
	PRDM8	ENST00000339711.8	TSL:1	c.1683C>T	p.Ser561Ser	synonymous	Exon 10 of 10	ENSP00000339764.4	Q9NQV8-1
	PRDM8	ENST00000952376.1		c.1686C>T	p.Ser562Ser	synonymous	Exon 4 of 4	ENSP00000622435.1

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2696 AN: 151656 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00675

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.0000737

Gnomad OTH AF: 0.0125

GnomAD2 exomes AF: 0.00375 AC: 559 AN: 149068 AF XY: 0.00286

Gnomad AFR exome AF: 0.0739

Gnomad AMR exome AF: 0.00285

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000708

GnomAD4 exome AF: 0.00181 AC: 2533 AN: 1402594 Hom.: 92 Cov.: 36 AF XY: 0.00155 AC XY: 1078 AN XY: 694462

African (AFR) AF: 0.0650 AC: 2040 AN: 31362

American (AMR) AF: 0.00348 AC: 133 AN: 38174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25270

East Asian (EAS) AF: 0.00 AC: 0 AN: 36282

South Asian (SAS) AF: 0.000247 AC: 20 AN: 80872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37140

Middle Eastern (MID) AF: 0.00416 AC: 22 AN: 5284

European-Non Finnish (NFE) AF: 0.0000505 AC: 55 AN: 1089744

Other (OTH) AF: 0.00450 AC: 263 AN: 58466

GnomAD4 genome AF: 0.0178 AC: 2702 AN: 151766 Hom.: 66 Cov.: 32 AF XY: 0.0171 AC XY: 1272 AN XY: 74204

African (AFR) AF: 0.0619 AC: 2564 AN: 41404

American (AMR) AF: 0.00674 AC: 103 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5080

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00347 AC: 1 AN: 288

European-Non Finnish (NFE) AF: 0.0000737 AC: 5 AN: 67832

Other (OTH) AF: 0.0123 AC: 26 AN: 2108

Alfa AF: 0.0105 Hom.: 9

Bravo AF: 0.0199

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Early-onset Lafora body disease (1)
-	-	1	not provided (1)
-	-	1	PRDM8-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.7
DANN	Benign	0.89
PhyloP100		-0.71
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs150632206; hg19: chr4-81124299;