CARHSP1 p.Arg35Arg

Variant names:

• chr16-8859223-C-C
• NM_014316.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr16-8859224--
• chr16-8859224-C-A
• chr16-8859224-C-G
• chr16-8859224-C-T
• chr16-8859226-G-T
• chr16-8859224-CCG-TCT

Variant summary

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

The NM_014316.4(CARHSP1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162
• 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]

LOC100130283 (HGNC:):

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.		exon_region	Exon 2 of 4	NP_055131.2	Q9Y2V2
	CARHSP1	NM_001042476.2		c.		exon_region	Exon 2 of 4	NP_001035941.1	Q9Y2V2
	CARHSP1	NM_001278260.2		c.		exon_region	Exon 3 of 5	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.		exon_region	Exon 2 of 4	ENSP00000311847.4	Q9Y2V2
	CARHSP1	ENST00000396593.6	TSL:1	c.		exon_region	Exon 2 of 4	ENSP00000379838.2	Q9Y2V2
	CARHSP1	ENST00000561530.5	TSL:3	c.		exon_region	Exon 2 of 4	ENSP00000455284.1	Q9Y2V2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.16

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: chr16-8953080;