8-98123775-CAAAA-CAAAAAAA

Variant names:

• chr8-98123775-C-CAAA
• rs1274675081
• NM_001145860.2:c.142+309_142+311dupAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145860.2(POP1):​c.142+309_142+311dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 123,804 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 0.000016 (0 hom., cov: 21)
• Consequence: POP1 NM_001145860.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POP1	NM_001145860.2	c.142+309_142+311dupAAA		intron_variant	Intron 2 of 15	ENST00000401707.7	NP_001139332.1
POP1	NM_001145861.2	c.142+309_142+311dupAAA		intron_variant	Intron 2 of 15		NP_001139333.1
POP1	NM_015029.3	c.142+309_142+311dupAAA		intron_variant	Intron 2 of 15		NP_055844.2
POP1	XM_011516801.3	c.142+309_142+311dupAAA		intron_variant	Intron 2 of 11		XP_011515103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POP1	ENST00000401707.7	c.142+296_142+297insAAA		intron_variant	Intron 2 of 15	2	NM_001145860.2	ENSP00000385787.2
POP1	ENST00000349693.3	c.142+296_142+297insAAA		intron_variant	Intron 2 of 15	1		ENSP00000339529.3
POP1	ENST00000522319.5	c.142+296_142+297insAAA		intron_variant	Intron 2 of 4	4		ENSP00000428945.1

Frequencies

GnomAD3 genomes AF: 0.0000162 AC: 2 AN: 123804 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000345

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000162 AC: 2 AN: 123804 Hom.: 0 Cov.: 21 AF XY: 0.0000169 AC XY: 1 AN XY: 59280

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000345

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1274675081; hg19: chr8-99136003;