1-979668-G-A

Variant names:

• chr1-979668-G-A
• rs527439217
• NM_001394713.1:c.1362C>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BP6_Moderate BP7 BS2_Supporting

The NM_001394713.1(PERM1):​c.1362C>T​(p.Ala454Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 1,550,274 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (5 hom., cov: 35)
  • Exomes 𝑓: 0.0036 (23 hom.)
• Consequence: PERM1 NM_001394713.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.220

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-979668-G-A is Benign according to our data. Variant chr1-979668-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2637983.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.22 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 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	c.1362C>T	p.Ala454Ala	synonymous_variant	Exon 2 of 4	ENST00000433179.4	NP_001381642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PERM1	ENST00000433179.4	c.1362C>T	p.Ala454Ala	synonymous_variant	Exon 2 of 4	5	NM_001394713.1	ENSP00000414022.3
PERM1	ENST00000694917.1	c.1362C>T	p.Ala454Ala	synonymous_variant	Exon 2 of 4			ENSP00000511592.1
PERM1	ENST00000341290.6	c.1020C>T	p.Ala340Ala	synonymous_variant	Exon 3 of 5	2		ENSP00000343864.2

Frequencies

GnomAD3 genomes AF: 0.00349 AC: 531 AN: 152246 Hom.: 5 Cov.: 35

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0223

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00359

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00394 AC: 587 AN: 149142 Hom.: 6 AF XY: 0.00360 AC XY: 289 AN XY: 80274

Gnomad AFR exome AF: 0.000297

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.00430

Gnomad EAS exome AF: 0.0000928

Gnomad SAS exome AF: 0.000133

Gnomad FIN exome AF: 0.0179

Gnomad NFE exome AF: 0.00401

Gnomad OTH exome AF: 0.00234

GnomAD4 exome AF: 0.00362 AC: 5060 AN: 1397910 Hom.: 23 Cov.: 95 AF XY: 0.00356 AC XY: 2454 AN XY: 689438

Gnomad4 AFR exome AF: 0.000285

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.00520

Gnomad4 EAS exome AF: 0.000364

Gnomad4 SAS exome AF: 0.000101

Gnomad4 FIN exome AF: 0.0169

Gnomad4 NFE exome AF: 0.00356

Gnomad4 OTH exome AF: 0.00342

GnomAD4 genome AF: 0.00349 AC: 531 AN: 152364 Hom.: 5 Cov.: 35 AF XY: 0.00415 AC XY: 309 AN XY: 74506

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0223

Gnomad4 NFE AF: 0.00359

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00383 Hom.: 0

Bravo AF: 0.00197

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 01, 2023

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	-0.79
CADD	Benign	4.2
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs527439217; hg19: chr1-915048;