rs770208373

Variant names:

• chr10-63610328-T-A
• rs770208373
• NM_001001330.3:c.559T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001001330.3(REEP3):​c.559T>A​(p.Ser187Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,553,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: REEP3 NM_001001330.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.123
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.054778516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REEP3	NM_001001330.3	c.559T>A	p.Ser187Thr	missense_variant	Exon 6 of 8	ENST00000373758.5	NP_001001330.1
LOC105378329	XR_001747467.3	n.411+4249A>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REEP3	ENST00000373758.5	c.559T>A	p.Ser187Thr	missense_variant	Exon 6 of 8	1	NM_001001330.3	ENSP00000362863.4
REEP3	ENST00000634963.1	n.*143T>A		non_coding_transcript_exon_variant	Exon 4 of 6	5		ENSP00000489394.1
REEP3	ENST00000634963.1	n.*143T>A		3_prime_UTR_variant	Exon 4 of 6	5		ENSP00000489394.1

Frequencies

GnomAD3 genomes AF: 0.0000856 AC: 13 AN: 151904 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000436 AC: 7 AN: 160712 AF XY: 0.0000475

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000111

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000122 AC: 171 AN: 1401170 Hom.: 0 Cov.: 31 AF XY: 0.000116 AC XY: 80 AN XY: 691226

African (AFR) AF: 0.0000315 AC: 1 AN: 31696

American (AMR) AF: 0.00 AC: 0 AN: 35730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 36002

South Asian (SAS) AF: 0.00 AC: 0 AN: 79324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.000142 AC: 153 AN: 1079646

Other (OTH) AF: 0.000292 AC: 17 AN: 58252

GnomAD4 genome AF: 0.0000856 AC: 13 AN: 151904 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74154

African (AFR) AF: 0.00 AC: 0 AN: 41326

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.0000200 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.559T>A (p.S187T) alteration is located in exon 6 (coding exon 6) of the REEP3 gene. This alteration results from a T to A substitution at nucleotide position 559, causing the serine (S) at amino acid position 187 to be replaced by a threonine (T). 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	0.057
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.12
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.27
Sift	Benign	0.11	T
Sift4G	Benign	0.13	T
Polyphen		0.20	B
Vest4		0.078
MVP		0.81
MPC		0.32
ClinPred		0.22	T
GERP RS		4.9
Varity_R		0.083
gMVP		0.28
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs770208373; hg19: chr10-65370088; COSMIC: COSV53424658;