NM_152415.3:c.125+11_125+15delGCTGC

Variant names:

• chr8-17247378-TCGCTG-T
• rs1811338690
• NM_152415.3:c.125+11_125+15delGCTGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_152415.3(VPS37A):​c.125+11_125+15delGCTGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000405 in 988,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: VPS37A NM_152415.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.75
• 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]

CNOT7 (HGNC:14101): (CCR4-NOT transcription complex subunit 7) The protein encoded by this gene binds to an anti-proliferative protein, B-cell translocation protein 1, which negatively regulates cell proliferation. Binding of the two proteins, which is driven by phosphorylation of the anti-proliferative protein, causes signaling events in cell division that lead to changes in cell proliferation associated with cell-cell contact. The encoded protein downregulates the innate immune response and therefore provides a therapeutic target for enhancing its antimicrobial activity against foreign agents. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1 and X. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 8-17247378-TCGCTG-T is Benign according to our data. Variant chr8-17247378-TCGCTG-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2918221.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152415.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS37A	NM_152415.3	MANE Select	c.125+11_125+15delGCTGC		intron	N/A	NP_689628.2	Q8NEZ2-1
	VPS37A	NM_001363173.2		c.125+11_125+15delGCTGC		intron	N/A	NP_001350102.1	Q8NEZ2-1
	VPS37A	NM_001363167.1		c.125+11_125+15delGCTGC		intron	N/A	NP_001350096.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS37A	ENST00000324849.9	TSL:1 MANE Select	c.125+11_125+15delGCTGC		intron	N/A	ENSP00000318629.4	Q8NEZ2-1
	VPS37A	ENST00000521829.5	TSL:1	c.125+11_125+15delGCTGC		intron	N/A	ENSP00000429680.1	Q8NEZ2-2
	VPS37A	ENST00000967262.1		c.125+11_125+15delGCTGC		intron	N/A	ENSP00000637321.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000405 AC: 4 AN: 988038 Hom.: 0 AF XY: 0.00000828 AC XY: 4 AN XY: 482818

African (AFR) AF: 0.00 AC: 0 AN: 21498

American (AMR) AF: 0.00 AC: 0 AN: 27650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15120

East Asian (EAS) AF: 0.00 AC: 0 AN: 12888

South Asian (SAS) AF: 0.0000548 AC: 4 AN: 73030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2834

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 772678

Other (OTH) AF: 0.00 AC: 0 AN: 36352

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary spastic paraplegia 53 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs1811338690; hg19: chr8-17104887;