10-63598124-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001001330.3(REEP3):c.283C>G(p.Leu95Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,435,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

REEP3
NM_001001330.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

Publications

0 publications found

Variant links:

Genes affected

REEP3 (HGNC:23711): (receptor accessory protein 3) Predicted to enable microtubule binding activity. Involved in mitotic nuclear membrane reassembly. Predicted to be integral component of membrane. Predicted to be active in cytoplasmic microtubule; endoplasmic reticulum membrane; and endoplasmic reticulum tubular network. [provided by Alliance of Genome Resources, Apr 2022]

REEP3 links:

LOC105378329 (HGNC:):

LOC105378329 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29148635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REEP3	NM_001001330.3 link	c.283C>G	p.Leu95Val	missense_variant	Exon 4 of 8	ENST00000373758.5	NP_001001330.1	Q6NUK4-1X5DR89
REEP3	XM_011539501.3 link	c.283C>G	p.Leu95Val	missense_variant	Exon 4 of 6		XP_011537803.1	X5DP57
REEP3	XM_017015896.2 link	c.283C>G	p.Leu95Val	missense_variant	Exon 4 of 7		XP_016871385.1	X5DP57
LOC105378329	XR_001747467.3 link	n.412-2028G>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REEP3	ENST00000373758.5 link	c.283C>G	p.Leu95Val	missense_variant	Exon 4 of 8	1	NM_001001330.3	ENSP00000362863.4		Q6NUK4-1
REEP3	ENST00000634963.1 link	n.79C>G		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000489394.1		A0A0U1RR85

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000204

AC:

AN:

245184

AF XY:

0.0000300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000284

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1435222

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715606

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32854

American (AMR)

AF:

0.00

AC:

AN:

44364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25976

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39536

South Asian (SAS)

AF:

0.00

AC:

AN:

85378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088740

Other (OTH)

AF:

0.00

AC:

AN:

59476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 25, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.283C>G (p.L95V) alteration is located in exon 4 (coding exon 4) of the REEP3 gene. This alteration results from a C to G substitution at nucleotide position 283, causing the leucine (L) at amino acid position 95 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

Eigen

Benign

-0.074

Eigen_PC

Benign

0.069

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.84

M_CAP

Benign

0.047

MetaRNN

Benign

0.29

MetaSVM

Uncertain

0.060

MutationAssessor

Benign

1.2

PhyloP100

1.7

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.35

REVEL

Uncertain

0.30

Sift

Benign

0.40

Sift4G

Benign

0.50

Polyphen

0.72

Vest4

0.34

MutPred

0.43

Gain of methylation at K99 (P = 0.0601);

MVP

0.73

MPC

0.36

ClinPred

0.070

GERP RS

5.0

Varity_R

0.16

gMVP

0.76

Mutation Taster

=86/14

polymorphism

(source)

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

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10-63598124-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over