Genetic Variant NM_003105.6:c.3559_3561delTCTinsAGC (chr11-121577379-TCT-AGC) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is The variant received 1 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_ModerateB4_Supporting

The NM_003105.6(SORL1):c.3559_3561delTCTinsAGC (p.1188) variant causes a synonymous change. The gene SORL1 is a known oncogene (CancerMine: 1 oncogene citations). Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

SORL1
NM_003105.6 synonymous

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.16

Publications

0 publications found

Variant links:

Genes affected

SORL1 (HGNC:11185): (sortilin related receptor 1) This gene encodes a mosaic protein that belongs to at least two families: the vacuolar protein sorting 10 (VPS10) domain-containing receptor family, and the low density lipoprotein receptor (LDLR) family. The encoded protein also contains fibronectin type III repeats and an epidermal growth factor repeat. The encoded preproprotein is proteolytically processed to generate the mature receptor, which likely plays roles in endocytosis and sorting. Mutations in this gene may be associated with Alzheimer's disease. [provided by RefSeq, Feb 2016]

SORL1 Gene-Disease associations (from GenCC):

early-onset autosomal dominant Alzheimer disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SORL1 links:

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new If you want to explore the variant's impact on the transcript NM_003105.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 1 points.

Show applied only (2)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])
	B4Synonymous/intronic, no splicing impact		Synonymous/intronic variant outside canonical splice sites (B4 supporting); Synonymous variant — splicing impact not confirmed absent; B4 supporting [-1]

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_003105.6. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	SORL1 NM_003105.6	MANE Select	c.3559_3561delTCTinsAGC p.1188	synonymous	N/A	Prot: NP_003096.2 UniProt: Q92673

SORL1 NM_003105.6

MANE Select

HGVSc / HGVSpc.3559_3561delTCTinsAGCp.1188

Exon rankN/A

synonymous

Prot: NP_003096.2UniProt: Q92673

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
SORL1 ENST00000260197.12	TSL:1MANE Select	c.3559_3561delTCTinsAGC p.1188	synonymous	N/A	Prot: ENSP00000260197.6 UniProt: Q92673
SORL1 ENST00000905166.1		c.3559_3561delTCTinsAGC p.1188	synonymous	N/A	Prot: ENSP00000575225.1 UniProt: A0ACI8RW67
SORL1 ENST00000905167.1		c.3442_3444delTCTinsAGC p.1149	synonymous	N/A	Prot: ENSP00000575226.1 UniProt: A0ACI8S861

SORL1 ENST00000260197.12

TSL:1MANE Select

HGVSc / HGVSpc.3559_3561delTCTinsAGCp.1188

Exon rankN/A

synonymous

Prot: ENSP00000260197.6UniProt: Q92673

SORL1 ENST00000905166.1

HGVSc / HGVSpc.3559_3561delTCTinsAGCp.1188

Exon rankN/A

synonymous

Prot: ENSP00000575225.1UniProt: A0ACI8RW67

SORL1 ENST00000905167.1

HGVSc / HGVSpc.3442_3444delTCTinsAGCp.1149

Exon rankN/A

synonymous

Prot: ENSP00000575226.1UniProt: A0ACI8S861

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Uncertain	6.2

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence