Genetic Variant PERM1:c.-102G>A (chr1-981131-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001394713.1(PERM1):c.-102G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,549,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

PERM1
NM_001394713.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.920

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-981131-C-T is Benign according to our data. Variant chr1-981131-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3234236.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PERM1	NM_001394713.1 link	c.-102G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 4	ENST00000433179.4	NP_001381642.1
PERM1	NM_001394713.1 link	c.-102G>A		5_prime_UTR_variant	Exon 2 of 4	ENST00000433179.4	NP_001381642.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PERM1	ENST00000433179.4 link	c.-102G>A	5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 4	5	NM_001394713.1	ENSP00000414022.3	Q5SV97-1
PERM1	ENST00000433179.4 link	c.-102G>A	5_prime_UTR_variant	Exon 2 of 4	5	NM_001394713.1	ENSP00000414022.3	Q5SV97-1
PERM1	ENST00000694917.1 link	c.-18-84G>A	intron_variant	Intron 1 of 3			ENSP00000511592.1	Q5SV97-1
PERM1	ENST00000341290.6 link	c.30+6G>A	splice_region_variant, intron_variant	Intron 2 of 4	2		ENSP00000343864.2	Q5SV97-3

Frequencies

GnomAD3 genomes

AF:

0.000999

AC:

152

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00119

AC:

176

AN:

147934

Hom.:

AF XY:

0.000979

AC XY:

AN XY:

79650

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00224

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000446

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00164

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.00123

AC:

1724

AN:

1396840

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

842

AN XY:

688854

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.00334

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.000209

Gnomad4 NFE exome

AF:

0.00137

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.000999

AC:

152

AN:

152216

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0000964

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00134

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00106

Hom.:

Bravo

AF:

0.00127

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PERM1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.5

DANN

Benign

0.48

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over