3-39143801-C-T

Variant names:

• chr3-39143801-C-T
• NM_033027.4:c.1024G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033027.4(CSRNP1):​c.1024G>A​(p.Glu342Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E342V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSRNP1 NM_033027.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21
• Publications: 0 publications found

Genes affected

CSRNP1 (HGNC:14300): (cysteine and serine rich nuclear protein 1) This gene encodes a protein that localizes to the nucleus and expression of this gene is induced in response to elevated levels of axin. The Wnt signalling pathway, which is negatively regulated by axin, is important in axis formation in early development and impaired regulation of this signalling pathway is often involved in tumors. A decreased level of expression of this gene in tumors compared to the level of expression in their corresponding normal tissues suggests that this gene product has a tumor suppressor function. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090830386).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033027.4. 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
	CSRNP1	NM_033027.4	MANE Select	c.1024G>A	p.Glu342Lys	missense	Exon 5 of 5	NP_149016.2	Q96S65
	CSRNP1	NM_001320559.2		c.1084G>A	p.Glu362Lys	missense	Exon 5 of 5	NP_001307488.1
	CSRNP1	NM_001320560.2		c.1024G>A	p.Glu342Lys	missense	Exon 5 of 5	NP_001307489.1	Q96S65

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSRNP1	ENST00000273153.10	TSL:1 MANE Select	c.1024G>A	p.Glu342Lys	missense	Exon 5 of 5	ENSP00000273153.5	Q96S65
	CSRNP1	ENST00000514182.1	TSL:1	c.1024G>A	p.Glu342Lys	missense	Exon 5 of 5	ENSP00000422532.1	Q96S65
	CSRNP1	ENST00000909282.1		c.1024G>A	p.Glu342Lys	missense	Exon 5 of 5	ENSP00000579341.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.2
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.039
Sift	Benign	0.11	T
Sift4G	Benign	0.74	T
Polyphen		0.23	B
Vest4		0.11
MutPred		0.13		Gain of ubiquitination at E342 (P = 6e-04)
MVP		0.12
MPC		0.32
ClinPred		0.24	T
GERP RS		4.6
Varity_R		0.066
gMVP		0.31
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-39185292;