12-51064163-CG-GC

Variant names:

• chr12-51064163-CG-GC
• NM_030809.3:c.1214_1215delCGinsGC
• CSRNP2 p.Thr405Ser

Variant summary

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

The NM_030809.3(CSRNP2):​c.1214_1215delCGinsGC​(p.Thr405Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. T405A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSRNP2 NM_030809.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.14
• 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.

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.1214_1215delCGinsGC	p.Thr405Ser	missense	N/A	NP_110436.1	Q9H175
	LETMD1	NM_001351337.2		c.544-3099_544-3098delCGinsGC		intron	N/A	NP_001338266.1
	CSRNP2	NR_045072.2		n.1668_1669delCGinsGC		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.1214_1215delCGinsGC	p.Thr405Ser	missense	N/A	ENSP00000228515.1	Q9H175
	CSRNP2	ENST00000863897.1		c.1214_1215delCGinsGC	p.Thr405Ser	missense	N/A	ENSP00000533956.1
	CSRNP2	ENST00000863898.1		c.1214_1215delCGinsGC	p.Thr405Ser	missense	N/A	ENSP00000533957.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-51457946;