Variant 9-136412015-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015160.3(PMPCA):c.90C>T(p.Tyr30=) variant causes a synonymous change. The variant allele was found at a frequency of 0.17 in 1,608,390 control chromosomes in the GnomAD database, including 24,989 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1698 hom., cov: 33)

Exomes 𝑓: 0.17 ( 23291 hom. )

Consequence

PMPCA
NM_015160.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.92

Variant links:

Genes affected

PMPCA (HGNC:18667): (peptidase, mitochondrial processing subunit alpha) The protein encoded by this gene is found in the mitochondrion, where it represents the alpha subunit of a proteolytic heterodimer. This heterodimer is responsible for cleaving the transit peptide from nuclear-encoded mitochondrial proteins. Defects in this gene are a cause of spinocerebellar ataxia, autosomal recessive 2. [provided by RefSeq, Mar 2016]

PMPCA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 9-136412015-C-T is Benign according to our data. Variant chr9-136412015-C-T is described in ClinVar as [Benign]. Clinvar id is 1220620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PMPCA	NM_015160.3 linkuse as main transcript	c.90C>T	p.Tyr30=	synonymous_variant	2/13	ENST00000371717.8
PMPCA	XM_005266059.4 linkuse as main transcript	c.90C>T	p.Tyr30=	synonymous_variant	2/12
PMPCA	NM_001282944.2 linkuse as main transcript	c.-209C>T		5_prime_UTR_variant	2/12
PMPCA	NM_001282946.2 linkuse as main transcript	c.-209C>T		5_prime_UTR_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMPCA	ENST00000371717.8 linkuse as main transcript	c.90C>T	p.Tyr30=	synonymous_variant	2/13	1	NM_015160.3	P1	Q10713-1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20728

AN:

152112

Hom.:

1691

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0524

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.0945

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.167

AC:

41765

AN:

249804

Hom.:

3906

AF XY:

0.165

AC XY:

22260

AN XY:

135184

show subpopulations

Gnomad AFR exome

AF:

0.0504

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.143

Gnomad SAS exome

AF:

0.168

Gnomad FIN exome

AF:

0.0929

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.174

AC:

253425

AN:

1456160

Hom.:

23291

Cov.:

AF XY:

0.173

AC XY:

125691

AN XY:

724660

show subpopulations

Gnomad4 AFR exome

AF:

0.0465

Gnomad4 AMR exome

AF:

0.274

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.133

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.0970

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.136

AC:

20744

AN:

152230

Hom.:

1698

Cov.:

AF XY:

0.134

AC XY:

9984

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0524

Gnomad4 AMR

AF:

0.213

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.164

Gnomad4 FIN

AF:

0.0945

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.167

Hom.:

3608

Bravo

AF:

0.144

Asia WGS

AF:

0.156

AC:

543

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Autosomal recessive spinocerebellar ataxia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.0

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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