1-114718626-G-C

Variant names:

• chr1-114718626-G-C
• NM_001007553.3:c.2336C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001007553.3(CSDE1):​c.2336C>G​(p.Pro779Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSDE1 NM_001007553.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.53

Genes affected

CSDE1 (HGNC:29905): (cold shock domain containing E1) Enables RNA stem-loop binding activity. Involved in IRES-dependent viral translational initiation; nuclear-transcribed mRNA catabolic process, no-go decay; and stress granule assembly. Located in Golgi apparatus; cytosol; and plasma membrane. Part of CRD-mediated mRNA stability complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSDE1	NM_001007553.3	c.2336C>G	p.Pro779Arg	missense_variant	Exon 19 of 20	ENST00000358528.9	NP_001007554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSDE1	ENST00000358528.9	c.2336C>G	p.Pro779Arg	missense_variant	Exon 19 of 20	1	NM_001007553.3	ENSP00000351329.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

CSDE1-associated neurodevelopmental disorder Uncertain:1

Jun 11, 2021

New York Genome Center

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The de novo c.2336C>G (p.Pro779Arg) variant identified in the CSDE1 gene substitutes a very well conserved Proline for Arginine at amino acid779/799 (exon 19/20). This variant is absent from gnomAD(v3.1.1) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Damaging (SIFT; score:0.00) and Pathogenic (REVEL; score:0.758) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The full phenotypic and genotypic spectrum of CSDE1-associated neurodevelopmental syndrome has yet to be elucidated, however to date only nonsense, frameshift, and canonical splice variants have been reported. Given this, the c.2336C>G (p.Pro779Arg) variant is currently classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	.;.;.;D;.;T;.;D
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	.;D;.;.;D;D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.86	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.3	.;.;.;M;.;.;.;M
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-6.7	D;.;D;D;D;D;D;D
REVEL	Pathogenic	0.76
Sift	Pathogenic	0.0	D;.;D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D;D
Polyphen		1.0	.;.;.;D;.;.;.;D
Vest4		0.94
MutPred		0.54		.;.;.;Gain of MoRF binding (P = 0.004);.;.;.;Gain of MoRF binding (P = 0.004);
MVP		0.85
MPC		1.8
ClinPred		1.0	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.87
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-115261247;