19-39198070-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001001414.2(NCCRP1):​c.355C>T​(p.Pro119Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000162 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

NCCRP1
NM_001001414.2 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65
Variant links:
Genes affected
NCCRP1 (HGNC:33739): (NCCRP1, F-box associated domain containing) Predicted to contribute to ubiquitin protein ligase activity. Involved in positive regulation of cell population proliferation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18428147).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NCCRP1NM_001001414.2 linkc.355C>T p.Pro119Ser missense_variant Exon 2 of 6 ENST00000339852.5 NP_001001414.1 Q6ZVX7
NCCRP1XM_011526906.4 linkc.355C>T p.Pro119Ser missense_variant Exon 2 of 5 XP_011525208.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NCCRP1ENST00000339852.5 linkc.355C>T p.Pro119Ser missense_variant Exon 2 of 6 1 NM_001001414.2 ENSP00000342137.3 Q6ZVX7

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000323
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000195
AC:
49
AN:
251472
Hom.:
0
AF XY:
0.000235
AC XY:
32
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000229
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000161
AC:
236
AN:
1461632
Hom.:
0
Cov.:
32
AF XY:
0.000168
AC XY:
122
AN XY:
727120
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000441
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000154
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152312
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000323
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000266
Hom.:
0
Bravo
AF:
0.000155
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000189
AC:
23
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.355C>T (p.P119S) alteration is located in exon 2 (coding exon 2) of the NCCRP1 gene. This alteration results from a C to T substitution at nucleotide position 355, causing the proline (P) at amino acid position 119 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
Uncertain
0.38
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.39
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.083
T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-3.4
D
REVEL
Benign
0.18
Sift
Benign
0.18
T
Sift4G
Benign
0.21
T
Polyphen
1.0
D
Vest4
0.50
MVP
0.52
MPC
0.76
ClinPred
0.60
D
GERP RS
4.2
Varity_R
0.17
gMVP
0.55

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145929148; hg19: chr19-39688710; API