16-8859224-CCG-TCT

Variant names:

• chr16-8859224-CCG-TCT
• NM_014316.4:c.103_105delCGGinsAGA
• CARHSP1 p.36

Variant summary

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

The NM_014316.4(CARHSP1):​c.103_105delCGGinsAGA​(p.36) variant causes a synonymous change. 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.

• Frequency: Genomes: not found (cov: 23)
• Consequence: CARHSP1 NM_014316.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.67
• Publications: 0 publications found

Genes affected

CARHSP1 (HGNC:17150): (calcium regulated heat stable protein 1) Enables mRNA 3'-UTR binding activity. Predicted to be involved in regulation of mRNA stability. Predicted to be located in P granule and cytosol. Predicted to be active in cytoplasm. Predicted to colocalize with cytoplasmic exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

PMM2 (HGNC:9115): (phosphomannomutase 2) The protein encoded by this gene catalyzes the isomerization of mannose 6-phosphate to mannose 1-phosphate, which is a precursor to GDP-mannose necessary for the synthesis of dolichol-P-oligosaccharides. Mutations in this gene have been shown to cause defects in glycoprotein biosynthesis, which manifests as carbohydrate-deficient glycoprotein syndrome type I. [provided by RefSeq, Jul 2008]

PMM2 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation type I

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women's Health
• PMM2-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• hyperinsulinemic hypoglycemia with polycystic kidney disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

LOC100130283 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014316.4. 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
	CARHSP1	NM_014316.4	MANE Select	c.103_105delCGGinsAGA	p.36	synonymous	N/A	NP_055131.2	Q9Y2V2
	CARHSP1	NM_001042476.2		c.103_105delCGGinsAGA	p.36	synonymous	N/A	NP_001035941.1	Q9Y2V2
	CARHSP1	NM_001278260.2		c.103_105delCGGinsAGA	p.36	synonymous	N/A	NP_001265189.1	Q9Y2V2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARHSP1	ENST00000311052.10	TSL:1 MANE Select	c.103_105delCGGinsAGA	p.36	synonymous	N/A	ENSP00000311847.4	Q9Y2V2
	CARHSP1	ENST00000396593.6	TSL:1	c.103_105delCGGinsAGA	p.36	synonymous	N/A	ENSP00000379838.2	Q9Y2V2
	CARHSP1	ENST00000568968.1	TSL:2	c.129_131delCGGinsAGA	p.CysGly43*	stop_gained	N/A	ENSP00000455988.1	H3BQY0

Frequencies

GnomAD3 genomes Cov.: 23

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

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7

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: chr16-8953081;