9-136411878-C-T

Position:

• chr9-136411878-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015160.3(PMPCA):​c.72-119C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 688,802 control chromosomes in the GnomAD database, including 460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (336 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (124 hom.)
• Consequence: PMPCA NM_015160.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0230

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-136411878-C-T is Benign according to our data. Variant chr9-136411878-C-T is described in ClinVar as [Benign]. Clinvar id is 1262675.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMPCA	NM_015160.3	c.72-119C>T		intron_variant		ENST00000371717.8
PMPCA	NM_001282944.2	c.-227-119C>T		intron_variant
PMPCA	NM_001282946.2	c.-227-119C>T		intron_variant
PMPCA	XM_005266059.4	c.72-119C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMPCA	ENST00000371717.8	c.72-119C>T		intron_variant		1	NM_015160.3	P1

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5286 AN: 152160 Hom.: 335 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.00475 AC: 2548 AN: 536524 Hom.: 124 AF XY: 0.00403 AC XY: 1149 AN XY: 285370

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.00749

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000375

Gnomad4 FIN exome AF: 0.0000647

Gnomad4 NFE exome AF: 0.000481

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.0348 AC: 5297 AN: 152278 Hom.: 336 Cov.: 33 AF XY: 0.0341 AC XY: 2539 AN XY: 74466

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0179

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0165 Hom.: 19

Bravo AF: 0.0397

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs73670257; hg19: chr9-139306330;