rs12411988

Positions:

• chr10-63555637-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001330.3(REEP3):​c.33-10701G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,216 control chromosomes in the GnomAD database, including 1,400 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 0.12 (1400 hom., cov: 32)
• Consequence: REEP3 NM_001001330.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REEP3	NM_001001330.3	c.33-10701G>C		intron_variant		ENST00000373758.5	NP_001001330.1
REEP3	XM_011539501.3	c.33-10701G>C		intron_variant			XP_011537803.1
REEP3	XM_017015896.2	c.33-10701G>C		intron_variant			XP_016871385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REEP3	ENST00000373758.5	c.33-10701G>C		intron_variant		1	NM_001001330.3	ENSP00000362863	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18498 AN: 152098 Hom.: 1396 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.122 AC: 18517 AN: 152216 Hom.: 1400 Cov.: 32 AF XY: 0.124 AC XY: 9222 AN XY: 74404

Gnomad4 AFR AF: 0.0462

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.143

Alfa AF: 0.143 Hom.: 962

Bravo AF: 0.120

Asia WGS AF: 0.251 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.62

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: rs12411988; hg19: chr10-65315397;