Genetic Variant PERM1:p.Asp247Asp (chr1-980289-G-A) – 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.741C>T(p.Asp247Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,550,398 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 8 hom., cov: 34)

Exomes 𝑓: 0.0045 ( 17 hom. )

Consequence

PERM1
NM_001394713.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.542

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 1-980289-G-A is Benign according to our data. Variant chr1-980289-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3388072.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.542 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8 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.741C>T	p.Asp247Asp	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.741C>T	p.Asp247Asp	synonymous_variant	Exon 2 of 4	5	NM_001394713.1	ENSP00000414022.3	Q5SV97-1
PERM1	ENST00000694917.1 link	c.741C>T	p.Asp247Asp	synonymous_variant	Exon 2 of 4			ENSP00000511592.1	Q5SV97-1
PERM1	ENST00000341290.6 link	c.399C>T	p.Asp133Asp	synonymous_variant	Exon 3 of 5	2		ENSP00000343864.2	Q5SV97-3

Frequencies

GnomAD3 genomes

AF:

0.00496

AC:

755

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0203

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00532

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00478

AC:

722

AN:

151046

Hom.:

AF XY:

0.00466

AC XY:

378

AN XY:

81156

show subpopulations

Gnomad AFR exome

AF:

0.000296

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.00812

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000444

Gnomad FIN exome

AF:

0.0177

Gnomad NFE exome

AF:

0.00493

Gnomad OTH exome

AF:

0.00393

GnomAD4 exome

AF:

0.00448

AC:

6259

AN:

1398028

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

3054

AN XY:

689494

show subpopulations

Gnomad4 AFR exome

AF:

0.000791

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.00747

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000265

Gnomad4 FIN exome

AF:

0.0169

Gnomad4 NFE exome

AF:

0.00451

Gnomad4 OTH exome

AF:

0.00409

GnomAD4 genome

AF:

0.00496

AC:

755

AN:

152370

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

405

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000745

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0203

Gnomad4 NFE

AF:

0.00532

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00436

Hom.:

Bravo

AF:

0.00379

Asia WGS

AF:

0.00115

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

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PERM1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.4

DANN

Benign

0.23

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