rs148541461

Variant names:

• chr11-35432700-C-G
• rs148541461
• NM_001001991.3:c.1819G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-35432700-C-G
• chr11-35432700-C-T

Variant summary

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

The NM_001001991.3(PAMR1):​c.1819G>C​(p.Val607Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: PAMR1 NM_001001991.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.540

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11946288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAMR1	NM_001001991.3	c.1819G>C	p.Val607Leu	missense_variant	Exon 11 of 11	ENST00000619888.5	NP_001001991.1
PAMR1	NM_015430.4	c.1870G>C	p.Val624Leu	missense_variant	Exon 12 of 12		NP_056245.2
PAMR1	NM_001282675.2	c.1699G>C	p.Val567Leu	missense_variant	Exon 13 of 13		NP_001269604.1
PAMR1	NM_001282676.2	c.1486G>C	p.Val496Leu	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.1819G>C	p.Val607Leu	missense_variant	Exon 11 of 11	1	NM_001001991.3	ENSP00000483703.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 33

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74364

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: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	2.2
DANN	Benign	0.82
DEOGEN2	Benign	0.075	.;T;.;T;.;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.84	T;T;T;T;T;T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.2	.;L;.;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.030	.;.;.;.;.;N
REVEL	Benign	0.17
Sift4G	Benign	0.35	T;T;T;T;T;T
Polyphen		0.013	B;B;.;.;.;.
Vest4		0.14
MutPred		0.70		.;Gain of disorder (P = 0.2128);.;.;.;.;
MVP		0.52
ClinPred		0.072	T
GERP RS		2.6
Varity_R		0.21
gMVP		0.59

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: rs148541461; hg19: chr11-35454248;