rs12768534

chr10-63581137-G-Achr10-63581137-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001001330.3(REEP3):c.106-13641G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,904 control chromosomes in the GnomAD database, including 15,028 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 0.44 (15028 hom., cov: 32)
• Consequence: REEP3 NM_001001330.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REEP3	NM_001001330.3	c.106-13641G>A		intron_variant		ENST00000373758.5
REEP3	XM_011539501.3	c.106-13641G>A		intron_variant
REEP3	XM_017015896.2	c.106-13641G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REEP3	ENST00000373758.5	c.106-13641G>A		intron_variant		1	NM_001001330.3	P1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66968 AN: 151786 Hom.: 14992 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.442 AC: 67066 AN: 151904 Hom.: 15028 Cov.: 32 AF XY: 0.439 AC XY: 32605 AN XY: 74244

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.422

Alfa AF: 0.450 Hom.: 7803

Bravo AF: 0.438

Asia WGS AF: 0.356 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	16
Dann	Benign	0.71

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: rs12768534; hg19: chr10-65340897;