Variant 11-35432700-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001001991.3(PAMR1):c.1819G>A(p.Val607Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,608 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

PAMR1
NM_001001991.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.540

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059255093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAMR1	NM_001001991.3 linkuse as main transcript	c.1819G>A	p.Val607Met	missense_variant	11/11	ENST00000619888.5	NP_001001991.1	Q6UXH9-1
PAMR1	NM_015430.4 linkuse as main transcript	c.1870G>A	p.Val624Met	missense_variant	12/12		NP_056245.2	Q6UXH9-2
PAMR1	NM_001282675.2 linkuse as main transcript	c.1699G>A	p.Val567Met	missense_variant	13/13		NP_001269604.1	Q6UXH9A0A087WXE9B7Z4A8
PAMR1	NM_001282676.2 linkuse as main transcript	c.1486G>A	p.Val496Met	missense_variant	9/9		NP_001269605.1	Q6UXH9-3B7Z6E5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAMR1	ENST00000619888.5 linkuse as main transcript	c.1819G>A	p.Val607Met	missense_variant	11/11	1	NM_001001991.3	ENSP00000483703.1		Q6UXH9-1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000797

AC:

AN:

250948

Hom.:

AF XY:

0.0000959

AC XY:

AN XY:

135588

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461388

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000289

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.1870G>A (p.V624M) alteration is located in exon 12 (coding exon 12) of the PAMR1 gene. This alteration results from a G to A substitution at nucleotide position 1870, causing the valine (V) at amino acid position 624 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.23

CADD

Benign

9.3

DANN

Benign

0.90

DEOGEN2

Benign

0.11

.;T;.;T;.;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.72

T;T;T;T;T;T

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.059

T;T;T;T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.7

.;L;.;.;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

0.25

.;.;.;.;.;N

REVEL

Benign

0.17

Sift4G

Benign

0.11

T;T;T;T;T;T

Polyphen

0.029

B;B;.;.;.;.

Vest4

0.12

MVP

0.55

ClinPred

0.0068

GERP RS

2.6

Varity_R

0.11

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over