6-136845652-A-G

Variant names:

• chr6-136845652-A-G
• NM_000288.4:c.377A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000288.4(PEX7):​c.377A>G​(p.Gln126Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q126P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PEX7 NM_000288.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.55

Genes affected

PEX7 (HGNC:8860): (peroxisomal biogenesis factor 7) This gene encodes the cytosolic receptor for the set of peroxisomal matrix enzymes targeted to the organelle by the peroxisome targeting signal 2 (PTS2). Defects in this gene cause peroxisome biogenesis disorders (PBDs), which are characterized by multiple defects in peroxisome function. There are at least 14 complementation groups for PBDs, with more than one phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene have been associated with PBD complementation group 11 (PBD-CG11) disorders, rhizomelic chondrodysplasia punctata type 1 (RCDP1), and Refsum disease (RD). [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4039064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX7	NM_000288.4	c.377A>G	p.Gln126Arg	missense_variant	Exon 4 of 10	ENST00000318471.5	NP_000279.1
PEX7	NM_001410945.1	c.263A>G	p.Gln88Arg	missense_variant	Exon 4 of 10		NP_001397874.1
PEX7	XM_047418874.1	c.377A>G	p.Gln126Arg	missense_variant	Exon 4 of 6		XP_047274830.1
PEX7	XM_006715502.3	c.339+19183A>G		intron_variant	Intron 3 of 6		XP_006715565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX7	ENST00000318471.5	c.377A>G	p.Gln126Arg	missense_variant	Exon 4 of 10	1	NM_000288.4	ENSP00000315680.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459428 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	0.17	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.37
Sift	Benign	0.34	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.69	.;P
Vest4		0.48
MutPred		0.54		Gain of MoRF binding (P = 0.033);Gain of MoRF binding (P = 0.033);
MVP		0.99
MPC		0.31
ClinPred		0.87	D
GERP RS		5.9
Varity_R		0.19
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-137166790;