20-4724969-T-A

Variant names:

• chr20-4724969-T-A
• NM_012409.4:c.418T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_012409.4(PRND):​c.418T>A​(p.Cys140Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRND NM_012409.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64
• Publications: 0 publications found

Genes affected

PRND (HGNC:15748): (prion like protein doppel) This gene is found on chromosome 20, approximately 20 kbp downstream of the gene encoding cellular prion protein, to which it is biochemically and structurally similar. The protein encoded by this gene is a membrane glycosylphosphatidylinositol-anchored glycoprotein that is found predominantly in testis. Mutations in this gene may lead to neurological disorders. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.903

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012409.4. 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
	PRND	NM_012409.4	MANE Select	c.418T>A	p.Cys140Ser	missense	Exon 2 of 2	NP_036541.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRND	ENST00000305817.3	TSL:1 MANE Select	c.418T>A	p.Cys140Ser	missense	Exon 2 of 2	ENSP00000306900.2	Q9UKY0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.82	D
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-9.0	D
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.79		Loss of helix (P = 0.079)
MVP		0.71
MPC		0.45
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.88
gMVP		0.72
Mutation Taster		=38/62	disease causing

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

hg19: chr20-4705615;