10-63610281-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001001330.3(REEP3):c.512A>G(p.Gln171Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,582,212 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0067 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 14 hom. )

Consequence

REEP3
NM_001001330.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.26

Publications

3 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029705167).

BP6

Variant 10-63610281-A-G is Benign according to our data. Variant chr10-63610281-A-G is described in ClinVar as [Benign]. Clinvar id is 711535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0067 (1020/152318) while in subpopulation AFR AF = 0.0229 (950/41568). AF 95% confidence interval is 0.0216. There are 13 homozygotes in GnomAd4. There are 508 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REEP3	NM_001001330.3 link	c.512A>G	p.Gln171Arg	missense_variant	Exon 6 of 8	ENST00000373758.5	NP_001001330.1	Q6NUK4-1X5DR89
LOC105378329	XR_001747467.3 link	n.411+4296T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
REEP3	ENST00000373758.5 link	c.512A>G	p.Gln171Arg	missense_variant	Exon 6 of 8	1	NM_001001330.3	ENSP00000362863.4	Q6NUK4-1
REEP3	ENST00000634963.1 link	n.*96A>G		non_coding_transcript_exon_variant	Exon 4 of 6	5		ENSP00000489394.1	A0A0U1RR85
REEP3	ENST00000634963.1 link	n.*96A>G		3_prime_UTR_variant	Exon 4 of 6	5		ENSP00000489394.1	A0A0U1RR85

Frequencies

GnomAD3 genomes

AF:

0.00670

AC:

1019

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

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:

0.0000147

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00167

AC:

330

AN:

197796

AF XY:

0.00132

show subpopulations

Gnomad AFR exome

AF:

0.0242

Gnomad AMR exome

AF:

0.00138

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000476

Gnomad OTH exome

AF:

0.000192

GnomAD4 exome

AF:

0.000623

AC:

891

AN:

1429894

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

343

AN XY:

707976

show subpopulations

African (AFR)

AF:

0.0215

AC:

709

AN:

32918

American (AMR)

AF:

0.00145

AC:

AN:

39374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25484

East Asian (EAS)

AF:

0.00

AC:

AN:

38914

South Asian (SAS)

AF:

0.0000243

AC:

AN:

82140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51634

Middle Eastern (MID)

AF:

0.000873

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000247

AC:

AN:

1094326

Other (OTH)

AF:

0.00153

AC:

AN:

59378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

116

154

193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00670

AC:

1020

AN:

152318

Hom.:

Cov.:

AF XY:

0.00682

AC XY:

508

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0229

AC:

950

AN:

41568

American (AMR)

AF:

0.00379

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

134

179

224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00282

Hom.:

Bravo

AF:

0.00775

ESP6500AA

AF:

0.0216

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00178

AC:

213

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.015

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.8

PhyloP100

3.3

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

REVEL

Benign

0.19

Sift

Benign

0.50

Sift4G

Benign

0.55

Polyphen

0.20

Vest4

0.34

MVP

0.83

MPC

0.36

ClinPred

0.026

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.096

gMVP

0.35

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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10-63610281-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over