NM_001145860.2:c.142+310_142+311delAA

Variant names:

• chr8-98123775-CAA-C
• rs1274675081
• NM_001145860.2:c.142+310_142+311delAA

Variant summary

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

The NM_001145860.2(POP1):​c.142+310_142+311delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 123,762 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00015 (0 hom., cov: 21)
• Consequence: POP1 NM_001145860.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• 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: G2P, Labcorp Genetics (formerly Invitae)
• anauxetic dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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_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.142+310_142+311delAA		intron	N/A	NP_001139332.1	Q99575
	POP1	NM_001145861.2		c.142+310_142+311delAA		intron	N/A	NP_001139333.1	Q99575
	POP1	NM_015029.3		c.142+310_142+311delAA		intron	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.142+297_142+298delAA		intron	N/A	ENSP00000385787.2	Q99575
	POP1	ENST00000349693.3	TSL:1	c.142+297_142+298delAA		intron	N/A	ENSP00000339529.3	Q99575
	POP1	ENST00000916453.1		c.142+297_142+298delAA		intron	N/A	ENSP00000586512.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 18 AN: 123754 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.0000300

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000166

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000121

Gnomad OTH AF: 0.000602

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

GnomAD4 genome AF: 0.000145 AC: 18 AN: 123762 Hom.: 0 Cov.: 21 AF XY: 0.000186 AC XY: 11 AN XY: 59274

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000300 AC: 1 AN: 33338

American (AMR) AF: 0.000166 AC: 2 AN: 12030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2890

East Asian (EAS) AF: 0.00 AC: 0 AN: 4160

South Asian (SAS) AF: 0.00 AC: 0 AN: 3954

European-Finnish (FIN) AF: 0.00103 AC: 7 AN: 6806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000121 AC: 7 AN: 57938

Other (OTH) AF: 0.000597 AC: 1 AN: 1674

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24

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

dbSNP: rs1274675081; hg19: chr8-99136003;