1-114719648-T-C

Variant names:

• chr1-114719648-T-C
• NM_001007553.3:c.2147A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001007553.3(CSDE1):​c.2147A>G​(p.Glu716Gly) 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: 32)
• Consequence: CSDE1 NM_001007553.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.62

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.802

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSDE1	NM_001007553.3	c.2147A>G	p.Glu716Gly	missense_variant	Exon 18 of 20	ENST00000358528.9	NP_001007554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSDE1	ENST00000358528.9	c.2147A>G	p.Glu716Gly	missense_variant	Exon 18 of 20	1	NM_001007553.3	ENSP00000351329.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Mar 03, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	.;.;.;T;.;T;.;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	.;D;.;.;D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.80	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.6	.;.;.;M;.;.;.;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.4	D;.;D;D;D;D;D;D
REVEL	Uncertain	0.59
Sift	Benign	0.11	T;.;T;T;T;D;T;T
Sift4G	Benign	0.20	T;T;T;T;T;T;T;T
Polyphen		1.0	.;.;.;D;.;.;.;D
Vest4		0.90
MutPred		0.48		.;.;.;Loss of sheet (P = 0.0181);.;.;.;Loss of sheet (P = 0.0181);
MVP		0.80
MPC		1.5
ClinPred		0.94	D
GERP RS		6.2
Varity_R		0.32
gMVP		0.71

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: chr1-115262269;