Genetic Variant NM_001172173.2:c.784A>C (chr2-165678779-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001172173.2(CSRNP3):c.784A>C(p.Ile262Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. I262V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CSRNP3
NM_001172173.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.18

Publications

0 publications found

Variant links:

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]

CSRNP3 links:

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ACMG classification

Classification was made for transcript

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=0.3654993).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSRNP3	NM_001172173.2	MANE Select	c.784A>C	p.Ile262Leu	missense	Exon 7 of 7	NP_001165644.1	Q8WYN3-1
CSRNP3	NM_001439057.1		c.880A>C	p.Ile294Leu	missense	Exon 5 of 5	NP_001425986.1
CSRNP3	NM_024969.3		c.784A>C	p.Ile262Leu	missense	Exon 5 of 5	NP_079245.2	Q8WYN3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSRNP3	ENST00000651982.1	MANE Select	c.784A>C	p.Ile262Leu	missense	Exon 7 of 7	ENSP00000498841.1	Q8WYN3-1
CSRNP3	ENST00000342316.8	TSL:1	c.784A>C	p.Ile262Leu	missense	Exon 5 of 5	ENSP00000344042.4	Q8WYN3-1
CSRNP3	ENST00000409420.1	TSL:5	c.880A>C	p.Ile294Leu	missense	Exon 5 of 5	ENSP00000387195.1	J3KQ49

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111976

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

M_CAP

Benign

0.0051

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.75

PhyloP100

6.2

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.0

REVEL

Benign

0.17

Sift

Benign

0.12

Sift4G

Benign

0.43

Polyphen

0.74

Vest4

0.38

MutPred

0.19

Gain of catalytic residue at I262 (P = 0.0916)

MVP

0.12

MPC

0.93

ClinPred

0.85

GERP RS

5.6

Varity_R

0.29

gMVP

0.90

Mutation Taster

=80/20

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over