19-39197167-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001001414.2(NCCRP1):​c.185C>T​(p.Ala62Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000699 in 1,287,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

NCCRP1
NM_001001414.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.585
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.032689333).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NCCRP1NM_001001414.2 linkc.185C>T p.Ala62Val missense_variant Exon 1 of 6 ENST00000339852.5 NP_001001414.1 Q6ZVX7
NCCRP1XM_011526906.4 linkc.185C>T p.Ala62Val missense_variant Exon 1 of 5 XP_011525208.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NCCRP1ENST00000339852.5 linkc.185C>T p.Ala62Val missense_variant Exon 1 of 6 1 NM_001001414.2 ENSP00000342137.3 Q6ZVX7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000699
AC:
9
AN:
1287296
Hom.:
0
Cov.:
33
AF XY:
0.00000475
AC XY:
3
AN XY:
631722
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.0000552
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000480
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 06, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.185C>T (p.A62V) alteration is located in exon 1 (coding exon 1) of the NCCRP1 gene. This alteration results from a C to T substitution at nucleotide position 185, causing the alanine (A) at amino acid position 62 to be replaced by a valine (V). 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
Benign
0.079
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
8.2
DANN
Benign
0.97
DEOGEN2
Benign
0.039
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.029
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.033
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.34
N
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.080
N
REVEL
Benign
0.028
Sift
Benign
0.059
T
Sift4G
Benign
0.25
T
Polyphen
0.029
B
Vest4
0.078
MutPred
0.13
Loss of relative solvent accessibility (P = 0.0186);
MVP
0.040
MPC
1.3
ClinPred
0.36
T
GERP RS
-0.44
Varity_R
0.030
gMVP
0.12

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: rs889943123; hg19: chr19-39687807; API