NM_152415.3:c.787_789delAAAinsCAG

Variant names:

• chr8-17280101-AAA-CAG
• NM_152415.3:c.787_789delAAAinsCAG
• VPS37A p.Lys263Gln

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_152415.3(VPS37A):c.787_789delAAAinsCAG (p.Lys263Gln) variant causes a missense change. The gene VPS37A is a tumor suppressor gene (CancerMine: 1 TSG 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. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.K263Q: Uncertain_significance (ClinVar VariationId 569194, 2 stars)

• Frequency: Genomes: not found (cov: 32)
• Consequence: VPS37A NM_152415.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.92
• Publications: 0 publications found

Genes affected

VPS37A (HGNC:24928): (VPS37A subunit of ESCRT-I) This gene belongs to the VPS37 family, and encodes a component of the ESCRT-I (endosomal sorting complex required for transport I) protein complex, required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies. Expression of this gene is downregulated in hepatocellular carcinoma, and mutations in this gene are associated with autosomal recessive spastic paraplegia-53. A related pseudogene has been identified on chromosome 5. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

VPS37A Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 53

  Inheritance: AR Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet
• complex hereditary spastic paraplegia

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

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])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_152415.3. 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
	VPS37A NM_152415.3	MANE Select	c.787_789delAAAinsCAG p.Lys263Gln	missense	N/A	Prot: NP_689628.2 UniProt:
	VPS37A NM_001363173.2		c.787_789delAAAinsCAG p.Lys263Gln	missense	N/A	Prot: NP_001350102.1 UniProt:
	VPS37A NM_001363167.1		c.787_789delAAAinsCAG p.Lys263Gln	missense	N/A	Prot: NP_001350096.1

VPS37A NM_152415.3

MANE Select

HGVSc / HGVSpc.787_789delAAAinsCAGp.Lys263Gln

Exon rankN/A

missense

Prot: NP_689628.2UniProt: Q8NEZ2-1

VPS37A NM_001363173.2

HGVSc / HGVSpc.787_789delAAAinsCAGp.Lys263Gln

Exon rankN/A

missense

Prot: NP_001350102.1UniProt: Q8NEZ2-1

VPS37A NM_001363167.1

HGVSc / HGVSpc.787_789delAAAinsCAGp.Lys263Gln

Exon rankN/A

missense

Prot: NP_001350096.1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	VPS37A ENST00000324849.9	TSL:1MANE Select	c.787_789delAAAinsCAG p.Lys263Gln	missense	N/A	Prot: ENSP00000318629.4 UniProt:
	VPS37A ENST00000521829.5	TSL:1	c.712_714delAAAinsCAG p.Lys238Gln	missense	N/A	Prot: ENSP00000429680.1 UniProt:
	VPS37A ENST00000967262.1		c.895_897delAAAinsCAG p.Lys299Gln	missense	N/A	Prot: ENSP00000637321.1 UniProt:

VPS37A ENST00000324849.9

TSL:1MANE Select

HGVSc / HGVSpc.787_789delAAAinsCAGp.Lys263Gln

Exon rankN/A

missense

Prot: ENSP00000318629.4UniProt: Q8NEZ2-1

VPS37A ENST00000521829.5

TSL:1

HGVSc / HGVSpc.712_714delAAAinsCAGp.Lys238Gln

Exon rankN/A

missense

Prot: ENSP00000429680.1UniProt: Q8NEZ2-2

VPS37A ENST00000967262.1

HGVSc / HGVSpc.895_897delAAAinsCAGp.Lys299Gln

Exon rankN/A

missense

Prot: ENSP00000637321.1UniProt: A0ACI8VEW5

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:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Uncertain	6.9

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.

Other links and lift over

hg19: chr8-17137610;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar