NM_030809.3:c.1225C>G

Variant names:

• chr12-51064153-G-C
• rs1937859475
• NM_030809.3:c.1225C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030809.3(CSRNP2):​c.1225C>G​(p.Pro409Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CSRNP2 NM_030809.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13
• Publications: 0 publications found

Genes affected

CSRNP2 (HGNC:16006): (cysteine and serine rich nuclear protein 2) The protein encoded by this gene belongs to the CSRNP family of nuclear proteins that share conserved regions, including cysteine- and serine- rich regions, a basic domain, a transcriptional activation domain, and bind the sequence 'AGAGTG', thus have the hallmark of transcription factors. Studies in mice suggest that these genes may have redundant functions. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]

LETMD1 (HGNC:24241): (LETM1 domain containing 1) This gene encodes a mitochondrial outer membrane protein. It has a potential role in tumorigenesis, which may result from negative regulation of the p53 tumor suppressor gene. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12509668).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030809.3. 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
	CSRNP2	NM_030809.3	MANE Select	c.1225C>G	p.Pro409Ala	missense	Exon 5 of 5	NP_110436.1	Q9H175
	LETMD1	NM_001351337.2		c.544-3109G>C		intron	N/A	NP_001338266.1
	CSRNP2	NR_045072.2		n.1679C>G		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSRNP2	ENST00000228515.6	TSL:1 MANE Select	c.1225C>G	p.Pro409Ala	missense	Exon 5 of 5	ENSP00000228515.1	Q9H175
	CSRNP2	ENST00000863897.1		c.1225C>G	p.Pro409Ala	missense	Exon 6 of 6	ENSP00000533956.1
	CSRNP2	ENST00000863898.1		c.1225C>G	p.Pro409Ala	missense	Exon 6 of 6	ENSP00000533957.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 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: 53420

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.069
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	0.97
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.034
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.1
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.074
Sift	Benign	0.11	T
Sift4G	Benign	0.73	T
Polyphen		0.36	B
Vest4		0.078
MutPred		0.30		Gain of catalytic residue at Y411 (P = 5e-04)
MVP		0.082
MPC		1.0
ClinPred		0.65	D
GERP RS		4.9
Varity_R		0.081
gMVP		0.39
Mutation Taster		=81/19	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: rs1937859475; hg19: chr12-51457936;