12-51064153-G-C

Variant summary

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

The NM_030809.3(CSRNP2):​c.1225C>G​(p.Pro409Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,894 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: 0.0000021 ( 0 hom. )

Consequence

CSRNP2
NM_030809.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13
Variant links:
Genes affected
CSRNP2 (HGNC:16006): (cysteine and serine rich nuclear protein 2) The protein encoded by this gene belongs to the CSRNP family of nuclear proteins that share conserved regions, including cysteine- and serine- rich regions, a basic domain, a transcriptional activation domain, and bind the sequence 'AGAGTG', thus have the hallmark of transcription factors. Studies in mice suggest that these genes may have redundant functions. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]
LETMD1 (HGNC:24241): (LETM1 domain containing 1) This gene encodes a mitochondrial outer membrane protein. It has a potential role in tumorigenesis, which may result from negative regulation of the p53 tumor suppressor gene. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Aug 2011]

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=0.12509668).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSRNP2NM_030809.3 linkc.1225C>G p.Pro409Ala missense_variant Exon 5 of 5 ENST00000228515.6 NP_110436.1 Q9H175

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSRNP2ENST00000228515.6 linkc.1225C>G p.Pro409Ala missense_variant Exon 5 of 5 1 NM_030809.3 ENSP00000228515.1 Q9H175

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461894
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
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
Nov 03, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1225C>G (p.P409A) alteration is located in exon 5 (coding exon 4) of the CSRNP2 gene. This alteration results from a C to G substitution at nucleotide position 1225, causing the proline (P) at amino acid position 409 to be replaced by an alanine (A). 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
0.069
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
18
DANN
Uncertain
0.97
DEOGEN2
Benign
0.016
T
Eigen
Benign
-0.034
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.64
T
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.074
Sift
Benign
0.11
T
Sift4G
Benign
0.73
T
Polyphen
0.36
B
Vest4
0.078
MutPred
0.30
Gain of catalytic residue at Y411 (P = 5e-04);
MVP
0.082
MPC
1.0
ClinPred
0.65
D
GERP RS
4.9
Varity_R
0.081
gMVP
0.39

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: rs1937859475; hg19: chr12-51457936; API