8-98123401-C-G

Variant names:

• chr8-98123401-C-G
• rs926275861
• NM_001145860.2:c.64C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145860.2(POP1):​c.64C>G​(p.Leu22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POP1 NM_001145860.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11260122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POP1	NM_001145860.2	c.64C>G	p.Leu22Val	missense_variant	Exon 2 of 16	ENST00000401707.7	NP_001139332.1
POP1	NM_001145861.2	c.64C>G	p.Leu22Val	missense_variant	Exon 2 of 16		NP_001139333.1
POP1	NM_015029.3	c.64C>G	p.Leu22Val	missense_variant	Exon 2 of 16		NP_055844.2
POP1	XM_011516801.3	c.64C>G	p.Leu22Val	missense_variant	Exon 2 of 12		XP_011515103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POP1	ENST00000401707.7	c.64C>G	p.Leu22Val	missense_variant	Exon 2 of 16	2	NM_001145860.2	ENSP00000385787.2
POP1	ENST00000349693.3	c.64C>G	p.Leu22Val	missense_variant	Exon 2 of 16	1		ENSP00000339529.3
POP1	ENST00000522319.5	c.64C>G	p.Leu22Val	missense_variant	Exon 2 of 5	4		ENSP00000428945.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.78	T;.;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.7	.;M;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.99	N;N;N
REVEL	Benign	0.094
Sift	Uncertain	0.016	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.99	.;D;D
Vest4		0.46, 0.46
MutPred		0.24		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.53
MPC		0.70
ClinPred		0.73	D
GERP RS		0.70
Varity_R		0.064
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs926275861; hg19: chr8-99135629; COSMIC: COSV62893120;