22-41573774-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014460.4(CSDC2):​c.296C>T​(p.Ser99Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,828 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: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CSDC2
NM_014460.4 missense

Scores

11
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84
Variant links:
Genes affected
CSDC2 (HGNC:30359): (cold shock domain containing C2) Predicted to enable mRNA 3'-UTR binding activity. Predicted to be involved in regulation of mRNA stability. Predicted to be located in nucleus. Predicted to be active 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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.911

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSDC2NM_014460.4 linkc.296C>T p.Ser99Phe missense_variant Exon 3 of 4 ENST00000306149.12 NP_055275.1 Q9Y534

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSDC2ENST00000306149.12 linkc.296C>T p.Ser99Phe missense_variant Exon 3 of 4 1 NM_014460.4 ENSP00000302485.7 Q9Y534
CSDC2ENST00000460790.1 linkc.245C>T p.Ser82Phe missense_variant Exon 2 of 3 3 ENSP00000417127.1 H7C4E7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1459828
Hom.:
0
Cov.:
30
AF XY:
0.00000826
AC XY:
6
AN XY:
726098
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:
0.00000720
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
Jun 21, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.296C>T (p.S99F) alteration is located in exon 3 (coding exon 2) of the CSDC2 gene. This alteration results from a C to T substitution at nucleotide position 296, causing the serine (S) at amino acid position 99 to be replaced by a phenylalanine (F). 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
0.99
BayesDel_addAF
Pathogenic
0.48
D
BayesDel_noAF
Pathogenic
0.45
CADD
Pathogenic
32
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.48
T;.
Eigen
Pathogenic
0.95
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Pathogenic
0.99
D;T
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.90
D;D
MetaSVM
Uncertain
0.63
D
MutationAssessor
Pathogenic
3.8
H;.
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-5.4
D;D
REVEL
Pathogenic
0.82
Sift
Benign
0.069
T;D
Sift4G
Uncertain
0.049
D;D
Polyphen
1.0
D;.
Vest4
0.98
MutPred
0.75
Loss of disorder (P = 0.0514);.;
MVP
0.77
MPC
1.4
ClinPred
1.0
D
GERP RS
5.2
Varity_R
0.77
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: chr22-41969778; API