rs767807537

Variant names:

• chr11-35434552-C-A
• rs767807537
• NM_001001991.3:c.1586G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-35434552-C-A
• chr11-35434552-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001001991.3(PAMR1):​c.1586G>T​(p.Arg529Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PAMR1 NM_001001991.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAMR1	NM_001001991.3	c.1586G>T	p.Arg529Leu	missense_variant	Exon 10 of 11	ENST00000619888.5	NP_001001991.1
PAMR1	NM_015430.4	c.1637G>T	p.Arg546Leu	missense_variant	Exon 11 of 12		NP_056245.2
PAMR1	NM_001282675.2	c.1466G>T	p.Arg489Leu	missense_variant	Exon 12 of 13		NP_001269604.1
PAMR1	NM_001282676.2	c.1253G>T	p.Arg418Leu	missense_variant	Exon 8 of 9		NP_001269605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAMR1	ENST00000619888.5	c.1586G>T	p.Arg529Leu	missense_variant	Exon 10 of 11	1	NM_001001991.3	ENSP00000483703.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.39
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;T;.;T;.;D
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.85	D;D;D;D;D;D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Benign	1.4	.;L;.;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.3	.;.;.;.;.;D
REVEL	Pathogenic	0.80
Sift4G	Benign	0.19	T;T;T;T;T;T
Polyphen		1.0	D;P;.;.;.;.
Vest4		0.84
MutPred		0.65		.;Loss of disorder (P = 0.0411);.;.;.;.;
MVP		0.66
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.54
gMVP		0.76

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: rs767807537; hg19: chr11-35456100;