NM_015160.3:c.6G>T

Variant names:

• chr9-136410674-G-T
• rs372181000
• NM_015160.3:c.6G>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_015160.3(PMPCA):​c.6G>T​(p.Ala2Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000488 in 1,413,944 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 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: PMPCA NM_015160.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.60
• Publications: 1 publications found

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]

ENTR1 (HGNC:10667): (endosome associated trafficking regulator 1) Involved in several processes, including endocytic recycling; positive regulation of cilium assembly; and positive regulation of protein localization to cilium. Located in endosome; microtubule organizing center; and midbody. Colocalizes with retromer complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 9-136410674-G-T is Benign according to our data. Variant chr9-136410674-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2889349.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.6 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015160.3. 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
	PMPCA	NM_015160.3	MANE Select	c.6G>T	p.Ala2Ala	synonymous	Exon 1 of 13	NP_055975.1	Q10713-1
	PMPCA	NM_001282946.2		c.-293G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	NP_001269875.1
	PMPCA	NM_001282944.2		c.-293G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_001269873.1	Q10713-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMPCA	ENST00000371717.8	TSL:1 MANE Select	c.6G>T	p.Ala2Ala	synonymous	Exon 1 of 13	ENSP00000360782.3	Q10713-1
	PMPCA	ENST00000622209.4	TSL:1	n.15G>T		non_coding_transcript_exon	Exon 1 of 5
	PMPCA	ENST00000444897.3	TSL:2	c.6G>T	p.Ala2Ala	synonymous	Exon 1 of 12	ENSP00000408393.2	Q5SXN9

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000582 AC: 7 AN: 120340 AF XY: 0.0000592

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000310

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000874

Gnomad NFE exome AF: 0.0000468

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000476 AC: 60 AN: 1261718 Hom.: 0 Cov.: 30 AF XY: 0.0000387 AC XY: 24 AN XY: 619614

African (AFR) AF: 0.0000389 AC: 1 AN: 25674

American (AMR) AF: 0.000338 AC: 6 AN: 17768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19242

East Asian (EAS) AF: 0.00 AC: 0 AN: 30956

South Asian (SAS) AF: 0.00 AC: 0 AN: 54714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39806

Middle Eastern (MID) AF: 0.000795 AC: 4 AN: 5030

European-Non Finnish (NFE) AF: 0.0000432 AC: 44 AN: 1017700

Other (OTH) AF: 0.0000984 AC: 5 AN: 50828

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74370

African (AFR) AF: 0.0000241 AC: 1 AN: 41462

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

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	-0.37
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		2.6
PromoterAI		-0.075	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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

Other links and lift over

dbSNP: rs372181000; hg19: chr9-139305126;