chr1-979313-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 14/18 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

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

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

Ensembl Transcripts

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

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

GnomAD2 exomes AF: 0.000330 AC: 46 AN: 139434 AF XY: 0.000308

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 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

African (AFR) AF: 0.000160 AC: 5 AN: 31212

American (AMR) AF: 0.00102 AC: 35 AN: 34364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24428

East Asian (EAS) AF: 0.0000281 AC: 1 AN: 35550

South Asian (SAS) AF: 0.00 AC: 0 AN: 77624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 0.000448 AC: 480 AN: 1070996

Other (OTH) AF: 0.000262 AC: 15 AN: 57308

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

African (AFR) AF: 0.0000962 AC: 4 AN: 41582

American (AMR) AF: 0.00209 AC: 32 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68012

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

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 v4.9

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
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.4
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.013
Sift	Benign	0.33	T
Sift4G	Benign	0.59	T
Vest4		0.080
MVP		0.19
ClinPred		0.037	T
GERP RS		-0.52
Varity_R		0.040
gMVP		0.056
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs536195330; hg19: chr1-914693;