5-150647992-A-C

Position:

• chr5-150647992-A-C

Variant summary

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

The ENST00000307662.5(SYNPO):​c.-284A>C variant causes a 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYNPO ENST00000307662.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.85

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_007286.6	c.-284A>C		5_prime_UTR_variant	2/3	ENST00000307662.5	NP_009217.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNPO	ENST00000307662.5	c.-284A>C		5_prime_UTR_variant	2/3	1	NM_007286.6	ENSP00000302139	P2

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

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.449A>C (p.K150T) alteration is located in exon 3 (coding exon 2) of the SYNPO gene. This alteration results from a A to C substitution at nucleotide position 449, causing the lysine (K) at amino acid position 150 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D;D
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	0.94	D;D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.49	T;T
Polyphen		1.0	D;D
Vest4		0.54
MutPred		0.22		Loss of ubiquitination at K150 (P = 6e-04);Loss of ubiquitination at K150 (P = 6e-04);
MVP		0.67
MPC		1.2
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.47
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-150027554;