17-48930569-GCCTGTAAGTC-TCCA

Position:

• chr17-48930569-GCCTGTAAGTC-TCCA

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_007241.4(SNF8):​c.673_683delGACTTACAGGCinsTGGA​(p.Asp225fs) variant causes a frameshift, missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNF8 NM_007241.4 frameshift, missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 9.96

Genes affected

SNF8 (HGNC:17028): (SNF8 subunit of ESCRT-II) The protein encoded by this gene is a component of the endosomal sorting complex required for transport II (ESCRT-II), which regulates the movement of ubiquitinylated transmembrane proteins to the lysosome for degradation. This complex also interacts with the RNA polymerase II elongation factor (ELL) to overcome the repressive effects of ELL on RNA polymerase II activity. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.134 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-48930569-GCCTGTAAGTC-TCCA is Pathogenic according to our data. Variant chr17-48930569-GCCTGTAAGTC-TCCA is described in ClinVar as [Pathogenic]. Clinvar id is 2664483.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNF8	NM_007241.4	c.673_683delGACTTACAGGCinsTGGA	p.Asp225fs	frameshift_variant, missense_variant	8/8	ENST00000502492.6	NP_009172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNF8	ENST00000502492.6	c.673_683delGACTTACAGGCinsTGGA	p.Asp225fs	frameshift_variant, missense_variant	8/8	1	NM_007241.4	ENSP00000421380.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder plus optic atrophy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 10, 2024

- -

SNF8-associated disease Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München

Dec 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-47007931;