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NM_007241.4(SNF8):c.572G>A (p.Gly191Asp) AND Developmental and epileptic encephalopathy 115

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 10, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003994557.1

Allele description [Variation Report for NM_007241.4(SNF8):c.572G>A (p.Gly191Asp)]

NM_007241.4(SNF8):c.572G>A (p.Gly191Asp)

Gene:
SNF8:SNF8 subunit of ESCRT-II [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.32
Genomic location:
Preferred name:
NM_007241.4(SNF8):c.572G>A (p.Gly191Asp)
HGVS:
  • NC_000017.11:g.48931710C>T
  • NM_001317192.2:c.569G>A
  • NM_001317193.2:c.521G>A
  • NM_001317194.2:c.260G>A
  • NM_007241.4:c.572G>AMANE SELECT
  • NP_001304121.1:p.Gly190Asp
  • NP_001304122.1:p.Gly174Asp
  • NP_001304123.1:p.Gly87Asp
  • NP_009172.2:p.Gly191Asp
  • NC_000017.10:g.47009072C>T
  • NR_133679.2:n.719G>A
Protein change:
G174D; GLY191ASP
Links:
OMIM: 610904.0001
Molecular consequence:
  • NM_001317192.2:c.569G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317193.2:c.521G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317194.2:c.260G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007241.4:c.572G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_133679.2:n.719G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Developmental and epileptic encephalopathy 115
Identifiers:
MONDO: MONDO:0968946; MedGen: CN377534; OMIM: 620783

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004812195OMIM
no assertion criteria provided
Pathogenic
(Apr 10, 2024) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy.

Brugger M, Lauri A, Zhen Y, Gramegna LL, Zott B, Sekulić N, Fasano G, Kopajtich R, Cordeddu V, Radio FC, Mancini C, Pizzi S, Paradisi G, Zanni G, Vasco G, Carrozzo R, Palombo F, Tonon C, Lodi R, La Morgia C, Arelin M, Blechschmidt C, et al.

Am J Hum Genet. 2024 Mar 7;111(3):594-613. doi: 10.1016/j.ajhg.2024.02.005. Epub 2024 Feb 28.

PubMed [citation]
PMID:
38423010
PMCID:
PMC10940020

Details of each submission

From OMIM, SCV004812195.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 2 sibs (patients A1 and A2) with developmental and epileptic encephalopathy-115 (DEE115; 620783), Brugger et al. (2024) identified compound heterozygous mutations in the SNF8 gene: a c.572G-A transition, resulting in a gly191-to-asp (G191D) substitution, and a c.501C-A transversion, resulting in a tyr167-to-ter (Y167X; 610904.0002) substitution. The mutations were identified by whole-exome sequencing and segregated with disease in the family. The G191D mutation was present in the gnomAD database (v4.0.0) at an allele frequency of 0.000003424, and the Y167X mutation was present in the gnomAD database (v4.0.0) at an allele frequency of 0.000001590. Proteomics in fibroblasts from one of the sibs demonstrated reduced expression of SNF8 as well as of 2 interacting subunits of ESCRT-II, VPS36 and VPS25.

In another patient (patient B1) with DEE15, Brugger et al. (2024) identified the G191D mutation in compound heterozygosity with a c.236C-T transition in SNF8, resulting in a pro79-to-leu (P79L; 610904.0003) substitution. The mutations were identified by whole-exome sequencing. The P79L mutation was present in the gnomAD database (v4.0.0) at an allele frequency of 0.00001179.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2024