chr12-51064348-C-G

Variant names:

• chr12-51064348-C-G
• NM_030809.3:c.1030G>C

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.1030G>C​(p.Gly344Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G344C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSRNP2 NM_030809.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.429
• 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=0.17569095).

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.1030G>C	p.Gly344Arg	missense	Exon 5 of 5	NP_110436.1	Q9H175
	LETMD1	NM_001351337.2		c.544-2914C>G		intron	N/A	NP_001338266.1
	CSRNP2	NR_045072.2		n.1484G>C		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.1030G>C	p.Gly344Arg	missense	Exon 5 of 5	ENSP00000228515.1	Q9H175
	CSRNP2	ENST00000863897.1		c.1030G>C	p.Gly344Arg	missense	Exon 6 of 6	ENSP00000533956.1
	CSRNP2	ENST00000863898.1		c.1030G>C	p.Gly344Arg	missense	Exon 6 of 6	ENSP00000533957.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.43
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.19
Sift	Benign	0.37	T
Sift4G	Benign	0.35	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.23		Gain of solvent accessibility (P = 0.006)
MVP		0.18
MPC		1.7
ClinPred		0.86	D
GERP RS		4.6
Varity_R		0.092
gMVP		0.26
Mutation Taster		=82/18	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

hg19: chr12-51458131;