NM_001367799.1:c.4620_4665+54delGCCCCGGCCTGCCGTCTTCCCTGTGCCCAGCTCTGCATACCCACAGGTGAGACCAGTGTTCTGCTGGGGGGTAAGGCATGGGAAAATACTGGGAATTCAT

Variant names:

• chr10-73799441-ACATGCCCCGGCCTGCCGTCTTCCCTGTGCCCAGCTCTGCATACCCACAGGTGAGACCAGTGTTCTGCTGGGGGGTAAGGCATGGGAAAATACTGGGAATT-A
• NM_001367799.1:c.4620_4665+54delGCCCCGGCCTGCCGTCTTCCCTGTGCCCAGCTCTGCATACCCACAGGTGAGACCAGTGTTCTGCTGGGGGGTAAGGCATGGGAAAATACTGGGAATTCAT

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001367799.1(ZSWIM8):​c.4620_4665+54delGCCCCGGCCTGCCGTCTTCCCTGTGCCCAGCTCTGCATACCCACAGGTGAGACCAGTGTTCTGCTGGGGGGTAAGGCATGGGAAAATACTGGGAATTCAT​(p.Pro1541ProfsTer37) variant causes a frameshift, splice donor, splice region, intron 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 Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSWIM8 NM_001367799.1 frameshift, splice_donor, splice_region, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54

Genes affected

ZSWIM8 (HGNC:23528): (zinc finger SWIM-type containing 8) Enables ubiquitin ligase-substrate adaptor activity. Involved in positive regulation of miRNA catabolic process; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ZSWIM8-AS1 (HGNC:45103): (ZSWIM8 antisense RNA 1)

ENSG00000272916 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM8	NM_001367799.1	c.4620_4665+54delGCCCCGGCCTGCCGTCTTCCCTGTGCCCAGCTCTGCATACCCACAGGTGAGACCAGTGTTCTGCTGGGGGGTAAGGCATGGGAAAATACTGGGAATTCAT	p.Pro1541ProfsTer37	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	Exon 21 of 26	ENST00000604729.6	NP_001354728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM8	ENST00000604729.6	c.4617_4665+51delCATGCCCCGGCCTGCCGTCTTCCCTGTGCCCAGCTCTGCATACCCACAGGTGAGACCAGTGTTCTGCTGGGGGGTAAGGCATGGGAAAATACTGGGAATT	p.His1539ProfsTer37	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	Exon 21 of 26	5	NM_001367799.1	ENSP00000474944.1
ENSG00000272916	ENST00000603027.5	n.*1432+962_*1432+1061delAATTCCCAGTATTTTCCCATGCCTTACCCCCCAGCAGAACACTGGTCTCACCTGTGGGTATGCAGAGCTGGGCACAGGGAAGACGGCAGGCCGGGGCATG		intron_variant	Intron 15 of 16	2		ENSP00000475031.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Sep 27, 2023

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Gene of Uncertain Significance -

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: chr10-75559199;