10-63598114-C-A

Variant names:

• chr10-63598114-C-A
• NM_001001330.3:c.273C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001001330.3(REEP3):​c.273C>A​(p.Phe91Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: REEP3 NM_001001330.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.352
• Publications: 0 publications found

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]

LOC105378329 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
REEP3	NM_001001330.3	c.273C>A	p.Phe91Leu	missense_variant	Exon 4 of 8	ENST00000373758.5	NP_001001330.1
REEP3	XM_011539501.3	c.273C>A	p.Phe91Leu	missense_variant	Exon 4 of 6		XP_011537803.1
REEP3	XM_017015896.2	c.273C>A	p.Phe91Leu	missense_variant	Exon 4 of 7		XP_016871385.1
LOC105378329	XR_001747467.3	n.412-2018G>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REEP3	ENST00000373758.5	c.273C>A	p.Phe91Leu	missense_variant	Exon 4 of 8	1	NM_001001330.3	ENSP00000362863.4
REEP3	ENST00000634963.1	n.69C>A		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000489394.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.273C>A (p.F91L) alteration is located in exon 4 (coding exon 4) of the REEP3 gene. This alteration results from a C to A substitution at nucleotide position 273, causing the phenylalanine (F) at amino acid position 91 to be replaced by a leucine (L). 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	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D
Eigen	Benign	-0.036
Eigen_PC	Benign	0.054
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	1.9	L
PhyloP100		0.35
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.43
Sift	Benign	0.052	T
Sift4G	Benign	0.094	T
Polyphen		0.63	P
Vest4		0.49
MutPred		0.51		Loss of ubiquitination at K90 (P = 0.0503);
MVP		0.86
MPC		0.51
ClinPred		0.94	D
GERP RS		3.1
Varity_R		0.51
gMVP		0.81
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

hg19: chr10-65357874;