rs2393989

Positions:

• chr10-63607136-T-A
• chr10-63607136-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
REEP3	NM_001001330.3	c.418-3051T>A		intron_variant		ENST00000373758.5	NP_001001330.1
REEP3	XM_011539501.3	c.*7425T>A		3_prime_UTR_variant	6/6		XP_011537803.1
REEP3	XM_017015896.2	c.*5752T>A		3_prime_UTR_variant	7/7		XP_016871385.1
LOC105378329	XR_001747467.3	n.411+7441A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REEP3	ENST00000373758.5	c.418-3051T>A		intron_variant		1	NM_001001330.3	ENSP00000362863.4
REEP3	ENST00000634963.1	n.*2-3051T>A		intron_variant		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

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.603

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2393989; hg19: chr10-65366896;