Genetic Variant PERM1:p.Ala704Ala (chr1-978918-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBP6_ModerateBP7BS2_Supporting

The NM_001394713.1(PERM1):c.2112C>T(p.Ala704Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,505,802 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 35)

Exomes 𝑓: 0.0021 ( 8 hom. )

Consequence

PERM1
NM_001394713.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.429

Publications

0 publications found

Variant links:

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]

PERM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-978918-G-A is Benign according to our data. Variant chr1-978918-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2637981.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.429 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 8 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PERM1	NM_001394713.1	MANE Select	c.2112C>T	p.Ala704Ala	synonymous	Exon 2 of 4	NP_001381642.1	Q5SV97-1
PERM1	NM_001291366.2		c.2112C>T	p.Ala704Ala	synonymous	Exon 2 of 4	NP_001278295.1	Q5SV97-1
PERM1	NM_001369897.1		c.2112C>T	p.Ala704Ala	synonymous	Exon 2 of 4	NP_001356826.1	Q5SV97-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PERM1	ENST00000433179.4	TSL:5 MANE Select	c.2112C>T	p.Ala704Ala	synonymous	Exon 2 of 4	ENSP00000414022.3	Q5SV97-1
PERM1	ENST00000694917.1		c.2112C>T	p.Ala704Ala	synonymous	Exon 2 of 4	ENSP00000511592.1	Q5SV97-1
PERM1	ENST00000880868.1		c.2112C>T	p.Ala704Ala	synonymous	Exon 3 of 5	ENSP00000550927.1

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

179

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00213

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00133

AC:

149

AN:

112140

AF XY:

0.00136

show subpopulations

Gnomad AFR exome

AF:

0.000329

Gnomad AMR exome

AF:

0.000326

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00238

Gnomad OTH exome

AF:

0.00123

GnomAD4 exome

AF:

0.00214

AC:

2894

AN:

1353484

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

1447

AN XY:

663170

show subpopulations

African (AFR)

AF:

0.000234

AC:

AN:

29924

American (AMR)

AF:

0.000346

AC:

AN:

28888

Ashkenazi Jewish (ASJ)

AF:

0.0000445

AC:

AN:

22490

East Asian (EAS)

AF:

0.00

AC:

AN:

35192

South Asian (SAS)

AF:

0.00331

AC:

243

AN:

73406

European-Finnish (FIN)

AF:

0.0000863

AC:

AN:

46372

Middle Eastern (MID)

AF:

0.00456

AC:

AN:

4822

European-Non Finnish (NFE)

AF:

0.00233

AC:

2460

AN:

1056594

Other (OTH)

AF:

0.00263

AC:

147

AN:

55796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

161

322

483

644

805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00117

AC:

178

AN:

152318

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41576

American (AMR)

AF:

0.000261

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00290

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00213

AC:

145

AN:

68004

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.00116

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.1

(source)

DANN

Benign

0.54

PhyloP100

0.43

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over