Genetic Variant PERM1:p.Gly573Arg (chr1-979313-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001394713.1(PERM1):c.1717G>A(p.Gly573Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000241 in 1,536,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

PERM1
NM_001394713.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.40

Publications

0 publications found

Variant links:

Genes affected

PERM1 (HGNC:28208): (PPARGC1 and ESRR induced regulator, muscle 1) Involved in response to muscle activity. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PERM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07034755).

BP6

Variant 1-979313-C-T is Benign according to our data. Variant chr1-979313-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3234418.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394713.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PERM1	NM_001394713.1	MANE Select	c.1717G>A	p.Gly573Arg	missense	Exon 2 of 4	NP_001381642.1	Q5SV97-1
PERM1	NM_001291366.2		c.1717G>A	p.Gly573Arg	missense	Exon 2 of 4	NP_001278295.1	Q5SV97-1
PERM1	NM_001369897.1		c.1717G>A	p.Gly573Arg	missense	Exon 2 of 4	NP_001356826.1	Q5SV97-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PERM1	ENST00000433179.4	TSL:5 MANE Select	c.1717G>A	p.Gly573Arg	missense	Exon 2 of 4	ENSP00000414022.3	Q5SV97-1
PERM1	ENST00000694917.1		c.1717G>A	p.Gly573Arg	missense	Exon 2 of 4	ENSP00000511592.1	Q5SV97-1
PERM1	ENST00000880868.1		c.1717G>A	p.Gly573Arg	missense	Exon 3 of 5	ENSP00000550927.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000143

AC:

AN:

139434

AF XY:

0.0000134

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000430

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000192

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1384630

Hom.:

Cov.:

AF XY:

0.0000308

AC XY:

AN XY:

681248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31212

American (AMR)

AF:

0.0000291

AC:

AN:

34364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24428

East Asian (EAS)

AF:

0.00

AC:

AN:

35550

South Asian (SAS)

AF:

0.0000386

AC:

AN:

77624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.0000280

AC:

AN:

1070996

Other (OTH)

AF:

0.0000174

AC:

AN:

57308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.00

Hom.:

Bravo

AF:

0.0000264

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.42

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.029

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.51

M_CAP

Benign

0.0052

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

PhyloP100

-1.4

PROVEAN

Benign

-2.2

REVEL

Benign

0.015

Sift

Benign

0.33

Sift4G

Benign

0.59

Vest4

0.080

MVP

0.19

ClinPred

0.054

GERP RS

-0.52

Varity_R

0.040

gMVP

0.056

Mutation Taster

=95/5

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

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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