rs1058450

chr4-119059485-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133477.3(SYNPO2):c.*1551C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,142 control chromosomes in the GnomAD database, including 1,573 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1573 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SYNPO2 NM_133477.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNPO2	NM_133477.3	c.*1551C>T		3_prime_UTR_variant	5/5	ENST00000307142.9
SYNPO2	NM_001286754.2	c.*1551C>T		3_prime_UTR_variant	5/5
SYNPO2	NM_001286755.2	c.*1970C>T		3_prime_UTR_variant	3/3
SYNPO2	NM_001389263.1	c.*1551C>T		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNPO2	ENST00000307142.9	c.*1551C>T		3_prime_UTR_variant	5/5	1	NM_133477.3	P1
SYNPO2	ENST00000504178.1	c.*1551C>T		3_prime_UTR_variant	4/4	1
SYNPO2	ENST00000448416.6	c.*1970C>T		3_prime_UTR_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19987 AN: 152024 Hom.: 1577 Cov.: 32

Gnomad AFR AF: 0.0564

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0836

Gnomad SAS AF: 0.0762

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.167

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.131 AC: 19971 AN: 152142 Hom.: 1573 Cov.: 32 AF XY: 0.130 AC XY: 9640 AN XY: 74378

Gnomad4 AFR AF: 0.0562

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.0832

Gnomad4 SAS AF: 0.0756

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.165

Alfa AF: 0.172 Hom.: 4727

Bravo AF: 0.128

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.8
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1058450; hg19: chr4-119980640;