1-978918-G-T

Variant names:

• chr1-978918-G-T
• rs570864131
• NM_001394713.1:c.2112C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001394713.1(PERM1):​c.2112C>A​(p.Ala704Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,353,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A704A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: PERM1 NM_001394713.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=0.429 with no splicing effect.

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.2112C>A	p.Ala704Ala	synonymous	Exon 2 of 4	NP_001381642.1	Q5SV97-1
	PERM1	NM_001291366.2		c.2112C>A	p.Ala704Ala	synonymous	Exon 2 of 4	NP_001278295.1	Q5SV97-1
	PERM1	NM_001369897.1		c.2112C>A	p.Ala704Ala	synonymous	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.2112C>A	p.Ala704Ala	synonymous	Exon 2 of 4	ENSP00000414022.3	Q5SV97-1
	PERM1	ENST00000694917.1		c.2112C>A	p.Ala704Ala	synonymous	Exon 2 of 4	ENSP00000511592.1	Q5SV97-1
	PERM1	ENST00000880868.1		c.2112C>A	p.Ala704Ala	synonymous	Exon 3 of 5	ENSP00000550927.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 7.39e-7 AC: 1 AN: 1353500 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 663182

African (AFR) AF: 0.00 AC: 0 AN: 29926

American (AMR) AF: 0.00 AC: 0 AN: 28888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22490

East Asian (EAS) AF: 0.0000284 AC: 1 AN: 35192

South Asian (SAS) AF: 0.00 AC: 0 AN: 73410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4822

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056604

Other (OTH) AF: 0.00 AC: 0 AN: 55796

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.71
DANN	Benign	0.49
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs570864131; hg19: chr1-914298;