Variant 11-35435974-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001001991.3(PAMR1):c.1262G>A(p.Arg421His) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,614,076 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

PAMR1
NM_001001991.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08

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 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=0.33934122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PAMR1	NM_001001991.3 linkuse as main transcript	c.1262G>A	p.Arg421His	missense_variant	9/11	ENST00000619888.5
PAMR1	NM_015430.4 linkuse as main transcript	c.1313G>A	p.Arg438His	missense_variant	10/12
PAMR1	NM_001282675.2 linkuse as main transcript	c.1142G>A	p.Arg381His	missense_variant	11/13
PAMR1	NM_001282676.2 linkuse as main transcript	c.929G>A	p.Arg310His	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAMR1	ENST00000619888.5 linkuse as main transcript	c.1262G>A	p.Arg421His	missense_variant	9/11	1	NM_001001991.3	P1	Q6UXH9-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251446

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Dec 16, 2023

The c.1313G>A (p.R438H) alteration is located in exon 10 (coding exon 10) of the PAMR1 gene. This alteration results from a G to A substitution at nucleotide position 1313, causing the arginine (R) at amino acid position 438 to be replaced by a histidine (H). 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

0.25

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0040

.;T;.;T;.;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.95

D;D;D;D;D;D

M_CAP

Benign

0.075

MetaRNN

Benign

0.34

T;T;T;T;T;T

MetaSVM

Uncertain

0.74

MutationAssessor

Benign

0.64

.;N;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

0.69

.;.;.;.;.;N

REVEL

Uncertain

0.53

Sift4G

Benign

0.49

T;T;T;T;T;T

Polyphen

0.37

B;D;.;.;.;.

Vest4

0.30

MutPred

0.48

.;Loss of MoRF binding (P = 0.0419);.;.;.;.;

MVP

0.77

ClinPred

0.24

GERP RS

5.5

Varity_R

0.43

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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