Genetic Variant PAMR1:p.Pro674Leu (chr11-35432498-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001001991.3(PAMR1):c.2021C>T(p.Pro674Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000576 in 1,614,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

PAMR1
NM_001001991.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

Publications

3 publications found

Variant links:

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]

PAMR1 links:

SLC1A2-AS2 (HGNC:40535): (SLC1A2 antisense RNA 2)

SLC1A2-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10761291).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001991.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAMR1	NM_001001991.3	MANE Select	c.2021C>T	p.Pro674Leu	missense	Exon 11 of 11	NP_001001991.1	Q6UXH9-1
PAMR1	NM_015430.4		c.2072C>T	p.Pro691Leu	missense	Exon 12 of 12	NP_056245.2	Q6UXH9-2
PAMR1	NM_001282675.2		c.1901C>T	p.Pro634Leu	missense	Exon 13 of 13	NP_001269604.1	A0A087WXE9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAMR1	ENST00000619888.5	TSL:1 MANE Select	c.2021C>T	p.Pro674Leu	missense	Exon 11 of 11	ENSP00000483703.1	Q6UXH9-1
PAMR1	ENST00000622144.4	TSL:1	c.2072C>T	p.Pro691Leu	missense	Exon 12 of 12	ENSP00000482899.1	Q6UXH9-2
PAMR1	ENST00000953162.1		c.2042C>T	p.Pro681Leu	missense	Exon 11 of 11	ENSP00000623221.1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000717

AC:

AN:

251190

AF XY:

0.0000589

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000568

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.000112

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.000227

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000567

AC:

AN:

1112010

Other (OTH)

AF:

0.0000497

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41584

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.099

Eigen

Benign

0.084

Eigen_PC

Benign

0.027

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.11

MetaSVM

Pathogenic

0.85

MutationAssessor

Uncertain

2.3

PhyloP100

4.8

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.48

REVEL

Uncertain

0.49

Sift4G

Benign

0.25

Polyphen

0.75

Vest4

0.28

MVP

0.75

ClinPred

0.20

GERP RS

4.4

Varity_R

0.18

gMVP

0.74

Mutation Taster

=77/23

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over