1-976215-A-T

Variant names:

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

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>A​(p.Val777Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• 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=0.24913087).

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>A	p.Val777Glu	missense	Exon 4 of 4	NP_001381642.1	Q5SV97-1
	PERM1	NM_001291366.2		c.2330T>A	p.Val777Glu	missense	Exon 4 of 4	NP_001278295.1	Q5SV97-1
	PERM1	NM_001369897.1		c.2330T>A	p.Val777Glu	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>A	p.Val777Glu	missense	Exon 4 of 4	ENSP00000414022.3	Q5SV97-1
	PERM1	ENST00000479361.1	TSL:1	n.198T>A		non_coding_transcript_exon	Exon 2 of 2
	PERM1	ENST00000694917.1		c.2330T>A	p.Val777Glu	missense	Exon 4 of 4	ENSP00000511592.1	Q5SV97-1

Frequencies

GnomAD3 genomes Cov.: 39

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 39

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.85	T
PhyloP100		0.054
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Vest4		0.50
MVP		0.39
ClinPred		0.80	D
GERP RS		2.1
Varity_R		0.20
gMVP		0.14
Mutation Taster		=80/20	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;