chr2-165676355-T-C

Variant names:

• chr2-165676355-T-C
• rs559756288
• NM_001172173.2:c.452T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001172173.2(CSRNP3):​c.452T>C​(p.Leu151Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CSRNP3 NM_001172173.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02
• Publications: 0 publications found

Genes affected

CSRNP3 (HGNC:30729): (cysteine and serine rich nuclear protein 3) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and sequence-specific DNA binding activity. Predicted to be involved in positive regulation of apoptotic process and positive regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4080606).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172173.2. 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
	CSRNP3	NM_001172173.2	MANE Select	c.452T>C	p.Leu151Pro	missense	Exon 6 of 7	NP_001165644.1	Q8WYN3-1
	CSRNP3	NM_001439057.1		c.548T>C	p.Leu183Pro	missense	Exon 4 of 5	NP_001425986.1
	CSRNP3	NM_024969.3		c.452T>C	p.Leu151Pro	missense	Exon 4 of 5	NP_079245.2	Q8WYN3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSRNP3	ENST00000651982.1	MANE Select	c.452T>C	p.Leu151Pro	missense	Exon 6 of 7	ENSP00000498841.1	Q8WYN3-1
	CSRNP3	ENST00000342316.8	TSL:1	c.452T>C	p.Leu151Pro	missense	Exon 4 of 5	ENSP00000344042.4	Q8WYN3-1
	CSRNP3	ENST00000409420.1	TSL:5	c.548T>C	p.Leu183Pro	missense	Exon 4 of 5	ENSP00000387195.1	J3KQ49

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251072 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461790 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111930

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74478

African (AFR) AF: 0.00 AC: 0 AN: 41546

American (AMR) AF: 0.00 AC: 0 AN: 15300

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	Pathogenic	1.0
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		8.0
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.38
Sift	Benign	0.054	T
Sift4G	Uncertain	0.037	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.26		Loss of stability (P = 0.0029)
MVP		0.13
MPC		2.5
ClinPred		0.88	D
GERP RS		4.6
Varity_R		0.74
gMVP		0.65
Mutation Taster		=25/75	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs559756288; hg19: chr2-166532865;