4-119030492-ACA-GCG

Variant names:

• chr4-119030492-ACA-GCG
• NM_133477.3:c.1717_1719delACAinsGCG
• SYNPO2 p.Thr573Ala

Variant summary

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

The NM_133477.3(SYNPO2):​c.1717_1719delACAinsGCG​(p.Thr573Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SYNPO2 NM_133477.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488
• Publications: 0 publications found

Genes affected

SYNPO2 (HGNC:17732): (synaptopodin 2) Enables alpha-actinin binding activity and filamin binding activity. Involved in positive regulation of actin filament bundle assembly; positive regulation of cell migration; and regulation of Rho-dependent protein serine/threonine kinase activity. Located in several cellular components, including Z disc; focal adhesion; and stress fiber. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133477.3. 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
	SYNPO2	NM_133477.3	MANE Select	c.1717_1719delACAinsGCG	p.Thr573Ala	missense	N/A	NP_597734.2	Q9UMS6-2
	SYNPO2	NM_001286754.2		c.1624_1626delACAinsGCG	p.Thr542Ala	missense	N/A	NP_001273683.1	Q9UMS6-4
	SYNPO2	NM_001128934.3		c.1717_1719delACAinsGCG	p.Thr573Ala	missense	N/A	NP_001122406.1	Q9UMS6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO2	ENST00000307142.9	TSL:1 MANE Select	c.1717_1719delACAinsGCG	p.Thr573Ala	missense	N/A	ENSP00000306015.4	Q9UMS6-2
	SYNPO2	ENST00000610556.4	TSL:1	c.1624_1626delACAinsGCG	p.Thr542Ala	missense	N/A	ENSP00000484885.1	Q9UMS6-4
	SYNPO2	ENST00000504178.1	TSL:1	c.1570_1572delACAinsGCG	p.Thr524Ala	missense	N/A	ENSP00000425496.1	H0Y9Y3

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-119951647;