rs10884049

Variant names:

• chr10-104821124-G-A
• rs10884049
• NM_014978.3:c.628-21668G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-104821124-G-A
• chr10-104821124-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014978.3(SORCS3):​c.628-21668G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,950 control chromosomes in the GnomAD database, including 10,998 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 0.36 (10998 hom., cov: 32)
• Consequence: SORCS3 NM_014978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476
• Publications: 1 publications found

Genes affected

SORCS3 (HGNC:16699): (sortilin related VPS10 domain containing receptor 3) This gene encodes a type-I receptor transmembrane protein that is a member of the vacuolar protein sorting 10 receptor family. Proteins of this family are defined by a vacuolar protein sorting 10 domain at the N-terminus. The N-terminal segment of this domain has a consensus motif for proprotein convertase processing, and the C-terminal segment of this domain is characterized by ten conserved cysteine residues. The vacuolar protein sorting 10 domain is followed by a leucine-rich segment, a transmembrane domain, and a short C-terminal cytoplasmic domain that interacts with adaptor molecules. The transcript is expressed at high levels in the brain, and candidate gene studies suggest that genetic variation in this gene is associated with Alzheimer's disease. Consistent with this observation, knockdown of the gene in cell culture results in an increase in amyloid precursor protein processing. [provided by RefSeq, Dec 2014]

SORCS3 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS3	NM_014978.3	c.628-21668G>A		intron_variant	Intron 1 of 26	ENST00000369701.8	NP_055793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS3	ENST00000369701.8	c.628-21668G>A		intron_variant	Intron 1 of 26	1	NM_014978.3	ENSP00000358715.3

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55106 AN: 151832 Hom.: 10998 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.363 AC: 55116 AN: 151950 Hom.: 10998 Cov.: 32 AF XY: 0.369 AC XY: 27406 AN XY: 74276

African (AFR) AF: 0.204 AC: 8429 AN: 41414

American (AMR) AF: 0.493 AC: 7526 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1375 AN: 3466

East Asian (EAS) AF: 0.658 AC: 3393 AN: 5160

South Asian (SAS) AF: 0.369 AC: 1773 AN: 4800

European-Finnish (FIN) AF: 0.460 AC: 4861 AN: 10558

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26459 AN: 67966

Other (OTH) AF: 0.360 AC: 758 AN: 2106

Alfa AF: 0.374 Hom.: 2297

Bravo AF: 0.364

Asia WGS AF: 0.441 AC: 1537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.76
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10884049; hg19: chr10-106580882;