rs568513607

Variant names:

• chr1-980388-A-G
• rs568513607
• NM_001394713.1:c.642T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-980388-A-G
• chr1-980388-A-C
• chr1-980388-A-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BP6_Moderate BP7 BS2_Supporting

The NM_001394713.1(PERM1):​c.642T>C​(p.Pro214Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,550,044 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0046 (17 hom.)
• Consequence: PERM1 NM_001394713.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-980388-A-G is Benign according to our data. Variant chr1-980388-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2637984.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.301 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 17 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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>C	p.Pro214Pro	synonymous	Exon 2 of 4	NP_001381642.1	Q5SV97-1
	PERM1	NM_001291366.2		c.642T>C	p.Pro214Pro	synonymous	Exon 2 of 4	NP_001278295.1	Q5SV97-1
	PERM1	NM_001369897.1		c.642T>C	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>C	p.Pro214Pro	synonymous	Exon 2 of 4	ENSP00000414022.3	Q5SV97-1
	PERM1	ENST00000694917.1		c.642T>C	p.Pro214Pro	synonymous	Exon 2 of 4	ENSP00000511592.1	Q5SV97-1
	PERM1	ENST00000880868.1		c.642T>C	p.Pro214Pro	synonymous	Exon 3 of 5	ENSP00000550927.1

Frequencies

GnomAD3 genomes AF: 0.00330 AC: 503 AN: 152234 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000892

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00606

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00345 AC: 504 AN: 145948 AF XY: 0.00355

Gnomad AFR exome AF: 0.000611

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00907

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00208

Gnomad NFE exome AF: 0.00583

Gnomad OTH exome AF: 0.00237

GnomAD4 exome AF: 0.00456 AC: 6379 AN: 1397692 Hom.: 17 Cov.: 45 AF XY: 0.00449 AC XY: 3097 AN XY: 689324

African (AFR) AF: 0.000506 AC: 16 AN: 31594

American (AMR) AF: 0.00132 AC: 47 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00858 AC: 216 AN: 25180

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

South Asian (SAS) AF: 0.00191 AC: 151 AN: 79210

European-Finnish (FIN) AF: 0.00174 AC: 83 AN: 47832

Middle Eastern (MID) AF: 0.00323 AC: 18 AN: 5576

European-Non Finnish (NFE) AF: 0.00521 AC: 5616 AN: 1078900

Other (OTH) AF: 0.00400 AC: 232 AN: 57960

GnomAD4 genome AF: 0.00330 AC: 503 AN: 152352 Hom.: 1 Cov.: 34 AF XY: 0.00302 AC XY: 225 AN XY: 74502

African (AFR) AF: 0.000890 AC: 37 AN: 41588

American (AMR) AF: 0.000784 AC: 12 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4830

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00606 AC: 412 AN: 68018

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00462 Hom.: 0

Bravo AF: 0.00325

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.63
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;