1-979313-C-G

Variant names:

• chr1-979313-C-G
• rs536195330
• NM_001394713.1:c.1717G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394713.1(PERM1):​c.1717G>C​(p.Gly573Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 1,536,958 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00036 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00039 (1 hom.)
• Consequence: PERM1 NM_001394713.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057452023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PERM1	NM_001394713.1	c.1717G>C	p.Gly573Arg	missense_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.1717G>C	p.Gly573Arg	missense_variant	Exon 2 of 4	5	NM_001394713.1	ENSP00000414022.3
PERM1	ENST00000694917.1	c.1717G>C	p.Gly573Arg	missense_variant	Exon 2 of 4			ENSP00000511592.1
PERM1	ENST00000341290.6	c.1375G>C	p.Gly459Arg	missense_variant	Exon 3 of 5	2		ENSP00000343864.2

Frequencies

GnomAD3 genomes AF: 0.000361 AC: 55 AN: 152210 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

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: 0.000265

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000330 AC: 46 AN: 139434 Hom.: 0 AF XY: 0.000308 AC XY: 23 AN XY: 74740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000988

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000384

Gnomad OTH exome AF: 0.000743

GnomAD4 exome AF: 0.000387 AC: 536 AN: 1384630 Hom.: 1 Cov.: 79 AF XY: 0.000389 AC XY: 265 AN XY: 681248

Gnomad4 AFR exome AF: 0.000160

Gnomad4 AMR exome AF: 0.00102

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000281

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000448

Gnomad4 OTH exome AF: 0.000262

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152328 Hom.: 1 Cov.: 34 AF XY: 0.000349 AC XY: 26 AN XY: 74488

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000116 Hom.: 0

Bravo AF: 0.000540

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000194 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.10
DANN	Benign	0.90
DEOGEN2	Benign	0.029	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.0057	T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-2.2	N;.
REVEL	Benign	0.013
Sift	Benign	0.33	T;.
Sift4G	Benign	0.59	T;T
Vest4		0.080
MVP		0.19
ClinPred		0.037	T
GERP RS		-0.52
Varity_R		0.040
gMVP		0.056

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: rs536195330; hg19: chr1-914693;