NM_133477.3:c.*1551C>T

Variant names:

• chr4-119059485-C-T
• rs1058450
• NM_133477.3:c.*1551C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO2	NM_133477.3	MANE Select	c.*1551C>T		3_prime_UTR	Exon 5 of 5	NP_597734.2
	SYNPO2	NM_001286754.2		c.*1551C>T		3_prime_UTR	Exon 5 of 5	NP_001273683.1
	SYNPO2	NM_001389263.1		c.*1551C>T		3_prime_UTR	Exon 3 of 3	NP_001376192.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO2	ENST00000307142.9	TSL:1 MANE Select	c.*1551C>T		3_prime_UTR	Exon 5 of 5	ENSP00000306015.4
	SYNPO2	ENST00000504178.1	TSL:1	c.*1551C>T		3_prime_UTR	Exon 4 of 4	ENSP00000425496.1
	SYNPO2	ENST00000448416.6	TSL:2	c.*1970C>T		3_prime_UTR	Exon 3 of 3	ENSP00000412623.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0562 AC: 2334 AN: 41520

American (AMR) AF: 0.129 AC: 1969 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3470

East Asian (EAS) AF: 0.0832 AC: 430 AN: 5166

South Asian (SAS) AF: 0.0756 AC: 364 AN: 4812

European-Finnish (FIN) AF: 0.152 AC: 1606 AN: 10594

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12026 AN: 67978

Other (OTH) AF: 0.165 AC: 349 AN: 2114

Alfa AF: 0.162 Hom.: 6351

Bravo AF: 0.128

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.65
PhyloP100		0.0050
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1058450; hg19: chr4-119980640;