1-976215-A-C

Variant names:

• chr1-976215-A-C
• rs7417106
• NM_001394713.1:c.2330T>G

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.2330T>G​(p.Val777Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,846 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. V777A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 39)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PERM1 NM_001394713.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 14 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=0.19632694).

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.2330T>G	p.Val777Gly	missense	Exon 4 of 4	NP_001381642.1	Q5SV97-1
	PERM1	NM_001291366.2		c.2330T>G	p.Val777Gly	missense	Exon 4 of 4	NP_001278295.1	Q5SV97-1
	PERM1	NM_001369897.1		c.2330T>G	p.Val777Gly	missense	Exon 4 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.2330T>G	p.Val777Gly	missense	Exon 4 of 4	ENSP00000414022.3	Q5SV97-1
	PERM1	ENST00000479361.1	TSL:1	n.198T>G		non_coding_transcript_exon	Exon 2 of 2
	PERM1	ENST00000694917.1		c.2330T>G	p.Val777Gly	missense	Exon 4 of 4	ENSP00000511592.1	Q5SV97-1

Frequencies

GnomAD3 genomes Cov.: 39

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385846 Hom.: 0 Cov.: 66 AF XY: 0.00000146 AC XY: 1 AN XY: 683588

African (AFR) AF: 0.00 AC: 0 AN: 30848

American (AMR) AF: 0.00 AC: 0 AN: 32274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24422

East Asian (EAS) AF: 0.00 AC: 0 AN: 35670

South Asian (SAS) AF: 0.00 AC: 0 AN: 77858

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5472

European-Non Finnish (NFE) AF: 9.31e-7 AC: 1 AN: 1074418

Other (OTH) AF: 0.00 AC: 0 AN: 57348

GnomAD4 genome Cov.: 39

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.88	T
PhyloP100		0.054
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Vest4		0.33
MVP		0.41
ClinPred		0.65	D
GERP RS		2.1
Varity_R		0.082
gMVP		0.084
Mutation Taster		=79/21	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: rs7417106; hg19: chr1-911595;