chr1-980388-A-T

Variant names:

• chr1-980388-A-T
• rs568513607
• NM_001394713.1:c.642T>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.642T>A​(p.Pro214Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,692 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. P214P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PERM1 NM_001394713.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 1 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=-0.89).
• BP7: Synonymous conserved (PhyloP=0.301 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.642T>A	p.Pro214Pro	synonymous	Exon 2 of 4	NP_001381642.1	Q5SV97-1
	PERM1	NM_001291366.2		c.642T>A	p.Pro214Pro	synonymous	Exon 2 of 4	NP_001278295.1	Q5SV97-1
	PERM1	NM_001369897.1		c.642T>A	p.Pro214Pro	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.642T>A	p.Pro214Pro	synonymous	Exon 2 of 4	ENSP00000414022.3	Q5SV97-1
	PERM1	ENST00000694917.1		c.642T>A	p.Pro214Pro	synonymous	Exon 2 of 4	ENSP00000511592.1	Q5SV97-1
	PERM1	ENST00000880868.1		c.642T>A	p.Pro214Pro	synonymous	Exon 3 of 5	ENSP00000550927.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000137 AC: 2 AN: 145948 AF XY: 0.0000254

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397692 Hom.: 0 Cov.: 45 AF XY: 0.00000290 AC XY: 2 AN XY: 689324

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5576

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078900

Other (OTH) AF: 0.00 AC: 0 AN: 57960

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.75
PhyloP100		0.30
Mutation Taster		=100/0	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: rs568513607; hg19: chr1-915768;