5-150618595-AC-A

Position:

• chr5-150618595-AC-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000394243.5(SYNPO):​c.230del​(p.Pro77ArgfsTer34) variant causes a frameshift change involving the alteration of a non-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: SYNPO ENST00000394243.5 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.316

Genes affected

SYNPO (HGNC:30672): (synaptopodin) Synaptopodin is an actin-associated protein that may play a role in actin-based cell shape and motility. The name synaptopodin derives from the protein's associations with postsynaptic densities and dendritic spines and with renal podocytes (Mundel et al., 1997 [PubMed 9314539]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNPO	NM_001166208.2	c.230del	p.Pro77ArgfsTer34	frameshift_variant	2/3		NP_001159680.1
SYNPO	NM_001166209.2	c.230del	p.Pro77ArgfsTer34	frameshift_variant	2/3		NP_001159681.1
SYNPO	XM_006714755.4	c.230del	p.Pro77ArgfsTer34	frameshift_variant	2/4		XP_006714818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNPO	ENST00000394243.5	c.230del	p.Pro77ArgfsTer34	frameshift_variant	2/3	1		ENSP00000377789	A2
SYNPO	ENST00000522122.1	c.230del	p.Pro77ArgfsTer34	frameshift_variant	2/3	2		ENSP00000428378	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

SYNPO-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 19, 2023

The SYNPO c.230delC variant is predicted to result in a frameshift and premature protein termination (p.Pro77Argfs*34). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. To date, this gene hasn't been validated to be a disease causing gene even though variants in this gene have been reported in individuals with developmental delay, focal segmental glomerulosclerosis or periventricular nodular heterotopia (Bloss et al. 2015. PubMed ID: 25790160; Klämbt et al. 2021. PubMed ID: 33615071; Dai et al. 2010. PubMed ID: 19666657; Heinzen et al. 2018. PubMed ID: 29738522). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

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: chr5-149998157;