chr4-105938337-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001033047.3(NPNT):c.422G>T(p.Gly141Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
NPNT
NM_001033047.3 missense
NM_001033047.3 missense
Scores
7
8
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 9.48
Genes affected
NPNT (HGNC:27405): (nephronectin) Predicted to enable integrin binding activity. Predicted to be involved in several processes, including cell-cell adhesion mediated by integrin; positive regulation of ERK1 and ERK2 cascade; and positive regulation of osteoblast differentiation. Predicted to act upstream of or within positive regulation of transforming growth factor beta receptor signaling pathway. Located in extracellular exosome. Part of collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]
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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, 0.857
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPNT | NM_001033047.3 | c.422G>T | p.Gly141Val | missense_variant | 5/12 | ENST00000379987.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPNT | ENST00000379987.7 | c.422G>T | p.Gly141Val | missense_variant | 5/12 | 1 | NM_001033047.3 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152140Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250412Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135326
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461452Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727036
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GnomAD4 genome AF: 0.000164 AC: 25AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74444
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D
Polyphen
1.0, 0.92, 1.0
.;D;.;.;.;P;.;D
Vest4
0.98, 0.97, 0.94, 0.97, 0.98
MVP
MPC
0.38
ClinPred
D
GERP RS
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at