8-98140867-CCC-GCT

Variant names:

• chr8-98140867-CCC-GCT
• NM_001145860.2:c.1573_1575delCCCinsGCT
• POP1 p.Pro525Ala

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM5

The NM_001145860.2(POP1):​c.1573_1575delCCCinsGCT​(p.Pro525Ala) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P525S) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POP1 NM_001145860.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.55
• Publications: 0 publications found

Genes affected

POP1 (HGNC:30129): (POP1 homolog, ribonuclease P/MRP subunit) This gene encodes the protein subunit of two different small nucleolar ribonucleoprotein complexes: the endoribonuclease for mitochondrial RNA processing complex and the ribonuclease P complex. The encoded protein is a ribonuclease that localizes to the nucleus and functions in pre-RNA processing. This protein is also an autoantigen in patients suffering from connective tissue diseases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

POP1 Gene-Disease associations (from GenCC):

• anauxetic dysplasia 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• anauxetic dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr8-98140867-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 393588.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145860.2. 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
	POP1	NM_001145860.2	MANE Select	c.1573_1575delCCCinsGCT	p.Pro525Ala	missense	N/A	NP_001139332.1	Q99575
	POP1	NM_001145861.2		c.1573_1575delCCCinsGCT	p.Pro525Ala	missense	N/A	NP_001139333.1	Q99575
	POP1	NM_015029.3		c.1573_1575delCCCinsGCT	p.Pro525Ala	missense	N/A	NP_055844.2	Q99575

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POP1	ENST00000401707.7	TSL:2 MANE Select	c.1573_1575delCCCinsGCT	p.Pro525Ala	missense	N/A	ENSP00000385787.2	Q99575
	POP1	ENST00000349693.3	TSL:1	c.1573_1575delCCCinsGCT	p.Pro525Ala	missense	N/A	ENSP00000339529.3	Q99575
	POP1	ENST00000916453.1		c.1591_1593delCCCinsGCT	p.Pro531Ala	missense	N/A	ENSP00000586512.1

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		4.6

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: chr8-99153095;