NM_001001991.3:c.1712G>C

Variant names:

• chr11-35432807-C-G
• rs752627585
• NM_001001991.3:c.1712G>C

Variant summary

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

The NM_001001991.3(PAMR1):​c.1712G>C​(p.Arg571Pro) variant causes a missense 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: 33)
• Consequence: PAMR1 NM_001001991.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

Genes affected

PAMR1 (HGNC:24554): (peptidase domain containing associated with muscle regeneration 1) Predicted to enable calcium ion binding activity and serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

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
PAMR1	NM_001001991.3	c.1712G>C	p.Arg571Pro	missense_variant	Exon 11 of 11	ENST00000619888.5	NP_001001991.1
PAMR1	NM_015430.4	c.1763G>C	p.Arg588Pro	missense_variant	Exon 12 of 12		NP_056245.2
PAMR1	NM_001282675.2	c.1592G>C	p.Arg531Pro	missense_variant	Exon 13 of 13		NP_001269604.1
PAMR1	NM_001282676.2	c.1379G>C	p.Arg460Pro	missense_variant	Exon 9 of 9		NP_001269605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAMR1	ENST00000619888.5	c.1712G>C	p.Arg571Pro	missense_variant	Exon 11 of 11	1	NM_001001991.3	ENSP00000483703.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;T;.;T;.;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.72	D;D;D;D;D;D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Benign	1.1	.;L;.;.;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.1	.;.;.;.;.;N
REVEL	Uncertain	0.55
Sift4G	Uncertain	0.010	D;D;D;D;D;D
Polyphen		1.0	D;D;.;.;.;.
Vest4		0.58
MutPred		0.58		.;Loss of MoRF binding (P = 0.044);.;.;.;.;
MVP		0.74
ClinPred		0.90	D
GERP RS		5.6
Varity_R		0.88
gMVP		0.86

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: rs752627585; hg19: chr11-35454355;