10-63607136-T-A

Variant names:

• chr10-63607136-T-A
• rs2393989
• NM_001001330.3:c.418-3051T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001330.3(REEP3):​c.418-3051T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,094 control chromosomes in the GnomAD database, including 27,231 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (27231 hom., cov: 32)
• Consequence: REEP3 NM_001001330.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REEP3	NM_001001330.3	c.418-3051T>A		intron_variant	Intron 5 of 7	ENST00000373758.5	NP_001001330.1
REEP3	XM_011539501.3	c.*7425T>A		3_prime_UTR_variant	Exon 6 of 6		XP_011537803.1
REEP3	XM_017015896.2	c.*5752T>A		3_prime_UTR_variant	Exon 7 of 7		XP_016871385.1
LOC105378329	XR_001747467.3	n.411+7441A>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REEP3	ENST00000373758.5	c.418-3051T>A		intron_variant	Intron 5 of 7	1	NM_001001330.3	ENSP00000362863.4
REEP3	ENST00000634963.1	n.*2-3051T>A		intron_variant	Intron 3 of 5	5		ENSP00000489394.1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90416 AN: 151976 Hom.: 27217 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.603

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.595 AC: 90464 AN: 152094 Hom.: 27231 Cov.: 32 AF XY: 0.595 AC XY: 44240 AN XY: 74332

African (AFR) AF: 0.665 AC: 27559 AN: 41466

American (AMR) AF: 0.619 AC: 9461 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2014 AN: 3472

East Asian (EAS) AF: 0.543 AC: 2810 AN: 5172

South Asian (SAS) AF: 0.602 AC: 2905 AN: 4826

European-Finnish (FIN) AF: 0.581 AC: 6141 AN: 10574

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37515 AN: 67974

Other (OTH) AF: 0.603 AC: 1274 AN: 2112

Alfa AF: 0.584 Hom.: 3241

Bravo AF: 0.599

Asia WGS AF: 0.548 AC: 1910 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.69
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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: rs2393989; hg19: chr10-65366896;