chr2-165676396-A-G

Variant names:

• chr2-165676396-A-G
• NM_001172173.2:c.493A>G

Variant summary

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

The NM_001172173.2(CSRNP3):​c.493A>G​(p.Asn165Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,756 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CSRNP3 NM_001172173.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• 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=0.358958).

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.493A>G	p.Asn165Asp	missense	Exon 6 of 7	NP_001165644.1	Q8WYN3-1
	CSRNP3	NM_001439057.1		c.589A>G	p.Asn197Asp	missense	Exon 4 of 5	NP_001425986.1
	CSRNP3	NM_024969.3		c.493A>G	p.Asn165Asp	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.493A>G	p.Asn165Asp	missense	Exon 6 of 7	ENSP00000498841.1	Q8WYN3-1
	CSRNP3	ENST00000342316.8	TSL:1	c.493A>G	p.Asn165Asp	missense	Exon 4 of 5	ENSP00000344042.4	Q8WYN3-1
	CSRNP3	ENST00000409420.1	TSL:5	c.589A>G	p.Asn197Asp	missense	Exon 4 of 5	ENSP00000387195.1	J3KQ49

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461756 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727200

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: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

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: 0.00000360 AC: 4 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

EpiCase AF: 0.00

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	Uncertain	0.42
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.6
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Benign	0.12	T
Sift4G	Benign	0.51	T
Polyphen		0.99	D
Vest4		0.58
MutPred		0.27		Gain of disorder (P = 0.0405)
MVP		0.12
MPC		2.1
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.31
gMVP		0.53
Mutation Taster		=64/36	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

hg19: chr2-166532906;