rs1472050

Variant names:

• chr10-104735013-A-C
• rs1472050
• NM_014978.3:c.627+93059A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-104735013-A-C
• chr10-104735013-A-T

Variant summary

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

The NM_014978.3(SORCS3):​c.627+93059A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,172 control chromosomes in the GnomAD database, including 4,246 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 0.23 (4246 hom., cov: 32)
• Consequence: SORCS3 NM_014978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS3	NM_014978.3	c.627+93059A>C		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.627+93059A>C		intron_variant	Intron 1 of 26	1	NM_014978.3	ENSP00000358715.3

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35122 AN: 152054 Hom.: 4232 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.231 AC: 35154 AN: 152172 Hom.: 4246 Cov.: 32 AF XY: 0.231 AC XY: 17184 AN XY: 74388

African (AFR) AF: 0.208 AC: 8629 AN: 41520

American (AMR) AF: 0.301 AC: 4603 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3466

East Asian (EAS) AF: 0.248 AC: 1283 AN: 5170

South Asian (SAS) AF: 0.334 AC: 1611 AN: 4818

European-Finnish (FIN) AF: 0.197 AC: 2091 AN: 10596

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.231 AC: 15687 AN: 68004

Other (OTH) AF: 0.234 AC: 495 AN: 2114

Alfa AF: 0.224 Hom.: 518

Bravo AF: 0.234

Asia WGS AF: 0.348 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		1.1
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: rs1472050; hg19: chr10-106494771;