10-63566381-G-T

Variant names:

• chr10-63566381-G-T
• rs1000405867
• NM_001001330.3:c.76G>T

Variant summary

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

The NM_001001330.3(REEP3):​c.76G>T​(p.Ala26Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A26T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: REEP3 NM_001001330.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01
• 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]

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.76G>T	p.Ala26Ser	missense_variant	Exon 2 of 8	ENST00000373758.5	NP_001001330.1
REEP3	XM_011539501.3	c.76G>T	p.Ala26Ser	missense_variant	Exon 2 of 6		XP_011537803.1
REEP3	XM_017015896.2	c.76G>T	p.Ala26Ser	missense_variant	Exon 2 of 7		XP_016871385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REEP3	ENST00000373758.5	c.76G>T	p.Ala26Ser	missense_variant	Exon 2 of 8	1	NM_001001330.3	ENSP00000362863.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1400200 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 691508

African (AFR) AF: 0.00 AC: 0 AN: 32074

American (AMR) AF: 0.00 AC: 0 AN: 36212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25186

East Asian (EAS) AF: 0.00 AC: 0 AN: 37226

South Asian (SAS) AF: 0.00 AC: 0 AN: 79182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076772

Other (OTH) AF: 0.00 AC: 0 AN: 58098

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.75	D
Eigen	Benign	0.028
Eigen_PC	Benign	0.017
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.7	D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.055	T
Polyphen		0.0060	B
Vest4		0.61
MutPred		0.86		Gain of disorder (P = 0.0141);
MVP		0.88
MPC		0.56
ClinPred		0.98	D
GERP RS		0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.68
Mutation Taster		=54/46	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: rs1000405867; hg19: chr10-65326141; COSMIC: COSV53428068;