3-39143284-T-G

Variant names:

• chr3-39143284-T-G
• rs1218523455
• NM_033027.4:c.1541A>C

Variant summary

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

The NM_033027.4(CSRNP1):​c.1541A>C​(p.Tyr514Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y514F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSRNP1 NM_033027.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.55
• 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 2 ACMG points.

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

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.1541A>C	p.Tyr514Ser	missense	Exon 5 of 5	NP_149016.2	Q96S65
	CSRNP1	NM_001320559.2		c.1601A>C	p.Tyr534Ser	missense	Exon 5 of 5	NP_001307488.1
	CSRNP1	NM_001320560.2		c.1541A>C	p.Tyr514Ser	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.1541A>C	p.Tyr514Ser	missense	Exon 5 of 5	ENSP00000273153.5	Q96S65
	CSRNP1	ENST00000514182.1	TSL:1	c.1541A>C	p.Tyr514Ser	missense	Exon 5 of 5	ENSP00000422532.1	Q96S65
	CSRNP1	ENST00000909282.1		c.1541A>C	p.Tyr514Ser	missense	Exon 5 of 5	ENSP00000579341.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.29
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.033	D
Polyphen		0.98	D
Vest4		0.63
MutPred		0.38		Gain of glycosylation at Y514 (P = 0.0272)
MVP		0.77
MPC		1.1
ClinPred		0.92	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.40
Mutation Taster		=75/25	polymorphism

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

dbSNP: rs1218523455; hg19: chr3-39184775;