Genetic Variant CSDE1:p.Gln793Pro (chr1-114718188-T-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_001007553.3(CSDE1):c.2378A>C(p.Gln793Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000483 in 1,613,940 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

CSDE1
NM_001007553.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.78

Variant links:

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]

CSDE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000526 (8/152080) while in subpopulation NFE AF= 0.000118 (8/68012). AF 95% confidence interval is 0.0000584. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSDE1	NM_001007553.3 link	c.2378A>C	p.Gln793Pro	missense_variant	Exon 20 of 20	ENST00000358528.9	NP_001007554.1	O75534-1A0A024R0E2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSDE1	ENST00000358528.9 link	c.2378A>C	p.Gln793Pro	missense_variant	Exon 20 of 20	1	NM_001007553.3	ENSP00000351329.4		O75534-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251388

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727232

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:

0.0000621

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000421

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

May 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2516A>C (p.Q839P) alteration is located in exon 21 (coding exon 19) of the CSDE1 gene. This alteration results from a A to C substitution at nucleotide position 2516, causing the glutamine (Q) at amino acid position 839 to be replaced by a proline (P). 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

0.096

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;.;.;T;.;T;.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;D;.;.;D;D;D;D

M_CAP

Benign

0.0090

MetaRNN

Uncertain

0.63

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.8

.;.;.;L;.;.;.;L

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.44

N;.;N;N;N;N;N;N

REVEL

Uncertain

0.30

Sift

Benign

0.14

T;.;T;T;T;T;T;T

Sift4G

Benign

0.24

T;T;T;T;T;T;T;T

Polyphen

0.82

.;.;.;P;.;.;.;P

Vest4

0.75

MVP

0.87

MPC

1.8

ClinPred

0.38

GERP RS

5.4

Varity_R

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over