NM_000287.4:c.2814G>C

Variant names:

• chr6-42964464-C-G
• rs1129186
• NM_000287.4:c.2814G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000287.4(PEX6):​c.2814G>C​(p.Glu938Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E938E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PEX6 NM_000287.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520

Genes affected

PEX6 (HGNC:8859): (peroxisomal biogenesis factor 6) This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) family of ATPases. This member is a predominantly cytoplasmic protein, which plays a direct role in peroxisomal protein import and is required for PTS1 (peroxisomal targeting signal 1, a C-terminal tripeptide of the sequence ser-lys-leu) receptor activity. Mutations in this gene cause peroxisome biogenesis disorders of complementation group 4 and complementation group 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049241513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX6	NM_000287.4	c.2814G>C	p.Glu938Asp	missense_variant	Exon 17 of 17	ENST00000304611.13	NP_000278.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX6	ENST00000304611.13	c.2814G>C	p.Glu938Asp	missense_variant	Exon 17 of 17	1	NM_000287.4	ENSP00000303511.8
PEX6	ENST00000244546	c.*350G>C		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000244546.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	10
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	-0.17	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.24
Sift	Benign	0.22	T
Sift4G	Benign	0.69	T
Polyphen		0.0020	B
Vest4		0.060
MutPred		0.15		Gain of helix (P = 0.132);
MVP		0.89
MPC		0.13
ClinPred		0.60	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.096
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs1129186; hg19: chr6-42932202;