Variant chr11-35432798-G-A 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.1721C>T(p.Thr574Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,457,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PAMR1
NM_001001991.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.93

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:

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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=0.2914071).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PAMR1	NM_001001991.3 linkuse as main transcript	c.1721C>T	p.Thr574Ile	missense_variant	11/11	ENST00000619888.5
PAMR1	NM_015430.4 linkuse as main transcript	c.1772C>T	p.Thr591Ile	missense_variant	12/12
PAMR1	NM_001282675.2 linkuse as main transcript	c.1601C>T	p.Thr534Ile	missense_variant	13/13
PAMR1	NM_001282676.2 linkuse as main transcript	c.1388C>T	p.Thr463Ile	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAMR1	ENST00000619888.5 linkuse as main transcript	c.1721C>T	p.Thr574Ile	missense_variant	11/11	1	NM_001001991.3	P1	Q6UXH9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

247316

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

133906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1457100

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

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.:

ExAC

AF:

0.0000165

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

Jan 16, 2024

The c.1772C>T (p.T591I) alteration is located in exon 12 (coding exon 12) of the PAMR1 gene. This alteration results from a C to T substitution at nucleotide position 1772, causing the threonine (T) at amino acid position 591 to be replaced by an isoleucine (I). 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

0.18

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.10

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

D;D;D;D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.29

T;T;T;T;T;T

MetaSVM

Uncertain

0.51

MutationTaster

Benign

0.69

D;D;D;D

PrimateAI

Benign

0.39

Sift4G

Uncertain

0.031

D;D;D;T;D;D

Polyphen

0.045

B;B;.;.;.;.

Vest4

0.28

MutPred

0.39

.;Loss of sheet (P = 0.0817);.;.;.;.;

MVP

0.46

ClinPred

0.30

GERP RS

3.7

Varity_R

0.54

gMVP

0.49

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