1-114720582-A-T

Variant names:

• chr1-114720582-A-T
• NM_001007553.3:c.2009T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001007553.3(CSDE1):​c.2009T>A​(p.Ile670Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 8.70
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007553.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSDE1	NM_001007553.3	MANE Select	c.2009T>A	p.Ile670Asn	missense	Exon 17 of 20	NP_001007554.1	O75534-1
	CSDE1	NM_001242891.2		c.2147T>A	p.Ile716Asn	missense	Exon 18 of 21	NP_001229820.1	O75534-4
	CSDE1	NM_001130523.3		c.2054T>A	p.Ile685Asn	missense	Exon 17 of 20	NP_001123995.1	O75534-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSDE1	ENST00000358528.9	TSL:1 MANE Select	c.2009T>A	p.Ile670Asn	missense	Exon 17 of 20	ENSP00000351329.4	O75534-1
	CSDE1	ENST00000369530.5	TSL:1	c.2054T>A	p.Ile685Asn	missense	Exon 17 of 20	ENSP00000358543.1	O75534-3
	CSDE1	ENST00000438362.7	TSL:1	c.2009T>A	p.Ile670Asn	missense	Exon 18 of 21	ENSP00000407724.3	O75534-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L
PhyloP100		8.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.94	P
Vest4		0.87
MutPred		0.44		Loss of helix (P = 0.028)
MVP		0.61
MPC		1.4
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.82
gMVP		0.94
Mutation Taster		=12/88	disease causing

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

Other links and lift over

hg19: chr1-115263203;