1-976215-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001394713.1(PERM1):​c.2330T>C​(p.Val777Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,537,898 control chromosomes in the GnomAD database, including 477,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (40391 hom., cov: 39)
  • Exomes 𝑓: 0.79 (436932 hom.)
• Consequence: PERM1 NM_001394713.1 missense
• Clinical Significance: Benign criteria provided, single submitter P:2 B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.7831055E-7).
• BP6: Variant 1-976215-A-G is Benign according to our data. Variant chr1-976215-A-G is described in ClinVar as Benign. ClinVar VariationId is 1320032.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

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>C	p.Val777Ala	missense	Exon 4 of 4	NP_001381642.1	Q5SV97-1
	PERM1	NM_001291366.2		c.2330T>C	p.Val777Ala	missense	Exon 4 of 4	NP_001278295.1	Q5SV97-1
	PERM1	NM_001369897.1		c.2330T>C	p.Val777Ala	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>C	p.Val777Ala	missense	Exon 4 of 4	ENSP00000414022.3	Q5SV97-1
	PERM1	ENST00000479361.1	TSL:1	n.198T>C		non_coding_transcript_exon	Exon 2 of 2
	PERM1	ENST00000694917.1		c.2330T>C	p.Val777Ala	missense	Exon 4 of 4	ENSP00000511592.1	Q5SV97-1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108731 AN: 152134 Hom.: 40371 Cov.: 39

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.720

GnomAD2 exomes AF: 0.792 AC: 105790 AN: 133640 AF XY: 0.792

Gnomad AFR exome AF: 0.473

Gnomad AMR exome AF: 0.838

Gnomad ASJ exome AF: 0.751

Gnomad EAS exome AF: 0.944

Gnomad FIN exome AF: 0.818

Gnomad NFE exome AF: 0.791

Gnomad OTH exome AF: 0.759

GnomAD4 exome AF: 0.792 AC: 1097406 AN: 1385646 Hom.: 436932 Cov.: 66 AF XY: 0.791 AC XY: 540705 AN XY: 683468

African (AFR) AF: 0.469 AC: 14466 AN: 30820

American (AMR) AF: 0.827 AC: 26684 AN: 32250

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 18346 AN: 24406

East Asian (EAS) AF: 0.932 AC: 33242 AN: 35668

South Asian (SAS) AF: 0.775 AC: 60295 AN: 77836

European-Finnish (FIN) AF: 0.811 AC: 38524 AN: 47528

Middle Eastern (MID) AF: 0.677 AC: 3688 AN: 5450

European-Non Finnish (NFE) AF: 0.798 AC: 857650 AN: 1074352

Other (OTH) AF: 0.776 AC: 44511 AN: 57336

GnomAD4 genome AF: 0.715 AC: 108801 AN: 152252 Hom.: 40391 Cov.: 39 AF XY: 0.719 AC XY: 53496 AN XY: 74440

African (AFR) AF: 0.492 AC: 20433 AN: 41520

American (AMR) AF: 0.800 AC: 12242 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2671 AN: 3472

East Asian (EAS) AF: 0.937 AC: 4866 AN: 5192

South Asian (SAS) AF: 0.773 AC: 3734 AN: 4828

European-Finnish (FIN) AF: 0.813 AC: 8632 AN: 10614

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53855 AN: 68006

Other (OTH) AF: 0.724 AC: 1530 AN: 2112

Alfa AF: 0.762 Hom.: 13870

Bravo AF: 0.705

TwinsUK AF: 0.808 AC: 2997

ALSPAC AF: 0.801 AC: 3087

ExAC AF: 0.701 AC: 11810

Asia WGS AF: 0.819 AC: 2849 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Neutrophil inclusion bodies (1)
-	-	1	not specified (1)
1	-	-	Renal tubular epithelial cell apoptosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	7.8e-7	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.054
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.016
Sift	Uncertain	0.024	D
Sift4G	Benign	0.072	T
Vest4		0.046
ClinPred		0.018	T
GERP RS		2.1
Varity_R		0.040
gMVP		0.049
Mutation Taster		=89/11	polymorphism (auto)

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; COSMIC: COSV58020657; COSMIC: COSV58020657;