NM_001394713.1:c.1717G>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394713.1(PERM1):​c.1717G>T​(p.Gly573Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,384,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G573R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000017 (0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19049293).

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>T	p.Gly573Trp	missense	Exon 2 of 4	NP_001381642.1	Q5SV97-1
	PERM1	NM_001291366.2		c.1717G>T	p.Gly573Trp	missense	Exon 2 of 4	NP_001278295.1	Q5SV97-1
	PERM1	NM_001369897.1		c.1717G>T	p.Gly573Trp	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>T	p.Gly573Trp	missense	Exon 2 of 4	ENSP00000414022.3	Q5SV97-1
	PERM1	ENST00000694917.1		c.1717G>T	p.Gly573Trp	missense	Exon 2 of 4	ENSP00000511592.1	Q5SV97-1
	PERM1	ENST00000880868.1		c.1717G>T	p.Gly573Trp	missense	Exon 3 of 5	ENSP00000550927.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000173 AC: 24 AN: 1384630 Hom.: 0 Cov.: 79 AF XY: 0.0000161 AC XY: 11 AN XY: 681248

African (AFR) AF: 0.00 AC: 0 AN: 31212

American (AMR) AF: 0.00 AC: 0 AN: 34364

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

East Asian (EAS) AF: 0.00 AC: 0 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: 0.0000215 AC: 23 AN: 1070996

Other (OTH) AF: 0.0000174 AC: 1 AN: 57308

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.87	T
PhyloP100		-1.4
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.053
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.030	D
Vest4		0.24
MVP		0.25
ClinPred		0.84	D
GERP RS		-0.52
Varity_R		0.029
gMVP		0.082
Mutation Taster		=94/6	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;