rs10822184

chr10-63577393-T-Cchr10-63577393-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.105+10983T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,930 control chromosomes in the GnomAD database, including 17,869 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 0.48 (17869 hom., cov: 30)
• Consequence: REEP3 NM_001001330.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REEP3	NM_001001330.3	c.105+10983T>C		intron_variant		ENST00000373758.5
REEP3	XM_011539501.3	c.105+10983T>C		intron_variant
REEP3	XM_017015896.2	c.105+10983T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REEP3	ENST00000373758.5	c.105+10983T>C		intron_variant		1	NM_001001330.3	P1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72970 AN: 151812 Hom.: 17866 Cov.: 30

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.480 AC: 72977 AN: 151930 Hom.: 17869 Cov.: 30 AF XY: 0.480 AC XY: 35652 AN XY: 74242

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.505

Alfa AF: 0.399 Hom.: 1825

Bravo AF: 0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.6
Dann	Benign	0.58

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: rs10822184; hg19: chr10-65337153;