rs201834210

Variant names:

• chr3-39143710-G-A
• rs201834210
• NM_033027.4:c.1115C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033027.4(CSRNP1):​c.1115C>T​(p.Pro372Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000582 in 1,614,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000059 (0 hom.)
• Consequence: CSRNP1 NM_033027.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03635633).

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.1115C>T	p.Pro372Leu	missense	Exon 5 of 5	NP_149016.2	Q96S65
	CSRNP1	NM_001320559.2		c.1175C>T	p.Pro392Leu	missense	Exon 5 of 5	NP_001307488.1
	CSRNP1	NM_001320560.2		c.1115C>T	p.Pro372Leu	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.1115C>T	p.Pro372Leu	missense	Exon 5 of 5	ENSP00000273153.5	Q96S65
	CSRNP1	ENST00000514182.1	TSL:1	c.1115C>T	p.Pro372Leu	missense	Exon 5 of 5	ENSP00000422532.1	Q96S65
	CSRNP1	ENST00000909282.1		c.1115C>T	p.Pro372Leu	missense	Exon 5 of 5	ENSP00000579341.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152218 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000439 AC: 11 AN: 250536 AF XY: 0.0000295

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000588 AC: 86 AN: 1461888 Hom.: 0 Cov.: 82 AF XY: 0.0000688 AC XY: 50 AN XY: 727244

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000701 AC: 78 AN: 1112008

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152336 Hom.: 0 Cov.: 34 AF XY: 0.0000537 AC XY: 4 AN XY: 74496

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68028

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	0.070
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.54
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.027
Sift	Benign	0.23	T
Sift4G	Benign	0.28	T
Polyphen		0.012	B
Vest4		0.051
MutPred		0.17		Loss of glycosylation at P375 (P = 0.0515)
MVP		0.10
MPC		0.25
ClinPred		0.024	T
GERP RS		2.7
Varity_R		0.025
gMVP		0.14
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201834210; hg19: chr3-39185201;