Genetic Variant PERM1:p.Pro214Pro (chr1-980388-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBP6_ModerateBP7BS2_Supporting

The NM_001394713.1(PERM1):c.642T>C(p.Pro214Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,550,044 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0046 ( 17 hom. )

Consequence

PERM1
NM_001394713.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.301

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-980388-A-G is Benign according to our data. Variant chr1-980388-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2637984.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.301 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 17 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PERM1	NM_001394713.1 link	c.642T>C	p.Pro214Pro	synonymous_variant	Exon 2 of 4	ENST00000433179.4	NP_001381642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PERM1	ENST00000433179.4 link	c.642T>C	p.Pro214Pro	synonymous_variant	Exon 2 of 4	5	NM_001394713.1	ENSP00000414022.3	Q5SV97-1
PERM1	ENST00000694917.1 link	c.642T>C	p.Pro214Pro	synonymous_variant	Exon 2 of 4			ENSP00000511592.1	Q5SV97-1
PERM1	ENST00000341290.6 link	c.300T>C	p.Pro100Pro	synonymous_variant	Exon 3 of 5	2		ENSP00000343864.2	Q5SV97-3

Frequencies

GnomAD3 genomes

AF:

0.00330

AC:

503

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00606

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00345

AC:

504

AN:

145948

Hom.:

AF XY:

0.00355

AC XY:

279

AN XY:

78698

show subpopulations

Gnomad AFR exome

AF:

0.000611

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.00907

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.00208

Gnomad NFE exome

AF:

0.00583

Gnomad OTH exome

AF:

0.00237

GnomAD4 exome

AF:

0.00456

AC:

6379

AN:

1397692

Hom.:

Cov.:

AF XY:

0.00449

AC XY:

3097

AN XY:

689324

show subpopulations

Gnomad4 AFR exome

AF:

0.000506

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.00858

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00191

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.00521

Gnomad4 OTH exome

AF:

0.00400

GnomAD4 genome

AF:

0.00330

AC:

503

AN:

152352

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

225

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00606

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00462

Hom.:

Bravo

AF:

0.00325

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PERM1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.0

DANN

Benign

0.63

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