2-86251993-G-T

Variant names:

• chr2-86251993-G-T
• NM_001371279.1:c.381C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001371279.1(REEP1):​c.381C>A​(p.Asn127Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: REEP1 NM_001371279.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

Genes affected

REEP1 (HGNC:25786): (receptor accessory protein 1) This gene encodes a mitochondrial protein that functions to enhance the cell surface expression of odorant receptors. Mutations in this gene cause spastic paraplegia autosomal dominant type 31, a neurodegenerative disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REEP1	NM_001371279.1	c.381C>A	p.Asn127Lys	missense_variant	Exon 5 of 9	ENST00000538924.7	NP_001358208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REEP1	ENST00000538924.7	c.381C>A	p.Asn127Lys	missense_variant	Exon 5 of 9	5	NM_001371279.1	ENSP00000438346.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461718 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727160

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: 8.99e-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	Pathogenic	0.96
BayesDel_addAF	Benign	-0.0056	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.;.;.;.;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.29	N
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D;D
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.46	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.28	D
MutationAssessor	Uncertain	2.4	M;.;.;.;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.5	D;.;.;.;.;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.021	D;.;.;.;.;D;D
Sift4G	Uncertain	0.059	T;.;.;.;.;T;.
Polyphen		0.20	B;.;.;.;.;.;.
Vest4		0.91
MutPred		0.44		Gain of MoRF binding (P = 0.0217);.;.;Gain of MoRF binding (P = 0.0217);.;.;.;
MVP		0.35
MPC		1.9
ClinPred		0.99	D
GERP RS		-1.7
Varity_R		0.68
gMVP		0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-86479116;