10-63554951-G-C

Position:

• chr10-63554951-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.33-11387G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,950 control chromosomes in the GnomAD database, including 17,222 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 0.47 (17222 hom., cov: 31)
• Consequence: REEP3 NM_001001330.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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 (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REEP3	NM_001001330.3	c.33-11387G>C		intron_variant		ENST00000373758.5	NP_001001330.1
REEP3	XM_011539501.3	c.33-11387G>C		intron_variant			XP_011537803.1
REEP3	XM_017015896.2	c.33-11387G>C		intron_variant			XP_016871385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REEP3	ENST00000373758.5	c.33-11387G>C		intron_variant		1	NM_001001330.3	ENSP00000362863.4

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71624 AN: 151832 Hom.: 17180 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.472 AC: 71734 AN: 151950 Hom.: 17222 Cov.: 31 AF XY: 0.468 AC XY: 34799 AN XY: 74282

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.469

Alfa AF: 0.317 Hom.: 795

Bravo AF: 0.471

Asia WGS AF: 0.408 AC: 1420 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	3.2
DANN	Benign	0.61

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: rs2163188; hg19: chr10-65314711;