rs753313677

Variant names:

• chr11-35434706-C-G
• rs753313677
• NM_001001991.3:c.1432G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-35434706-C-G
• chr11-35434706-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001001991.3(PAMR1):​c.1432G>C​(p.Gly478Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PAMR1 NM_001001991.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32002068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAMR1	NM_001001991.3	c.1432G>C	p.Gly478Arg	missense_variant	Exon 10 of 11	ENST00000619888.5	NP_001001991.1
PAMR1	NM_015430.4	c.1483G>C	p.Gly495Arg	missense_variant	Exon 11 of 12		NP_056245.2
PAMR1	NM_001282675.2	c.1312G>C	p.Gly438Arg	missense_variant	Exon 12 of 13		NP_001269604.1
PAMR1	NM_001282676.2	c.1099G>C	p.Gly367Arg	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.1432G>C	p.Gly478Arg	missense_variant	Exon 10 of 11	1	NM_001001991.3	ENSP00000483703.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	.;T;.;T;.;T
Eigen	Benign	-0.089
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Uncertain	-0.044	T
MutationAssessor	Benign	1.5	.;L;.;.;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.15	.;.;.;.;.;N
REVEL	Uncertain	0.52
Sift4G	Uncertain	0.042	D;D;T;T;D;D
Polyphen		0.77	P;P;.;.;.;.
Vest4		0.39
MutPred		0.54		.;Gain of MoRF binding (P = 0.0043);.;.;.;.;
MVP		0.49
ClinPred		0.53	D
GERP RS		4.4
Varity_R		0.098
gMVP		0.47

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: rs753313677; hg19: chr11-35456254;