20-4724969-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_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

Scores

9
8
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRNDNM_012409.4 linkc.418T>A p.Cys140Ser missense_variant Exon 2 of 2 ENST00000305817.3 NP_036541.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRNDENST00000305817.3 linkc.418T>A p.Cys140Ser missense_variant Exon 2 of 2 1 NM_012409.4 ENSP00000306900.2 Q9UKY0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 05, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.418T>A (p.C140S) alteration is located in exon 2 (coding exon 1) of the PRND gene. This alteration results from a T to A substitution at nucleotide position 418, causing the cysteine (C) at amino acid position 140 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-4705615; API