10-73647884-G-A

Position:

• chr10-73647884-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001114133.3(SYNPO2L):​c.1768C>T​(p.Pro590Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYNPO2L NM_001114133.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0320

Genes affected

SYNPO2L (HGNC:23532): (synaptopodin 2 like) Predicted to enable actin binding activity. Predicted to be involved in several processes, including positive regulation of Rho protein signal transduction; positive regulation of stress fiber assembly; and sarcomere organization. Located in cell junction; cytosol; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038157254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNPO2L	NM_001114133.3	c.1768C>T	p.Pro590Ser	missense_variant	4/4	ENST00000394810.3	NP_001107605.1
SYNPO2L	NM_024875.5	c.1096C>T	p.Pro366Ser	missense_variant	2/2		NP_079151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNPO2L	ENST00000394810.3	c.1768C>T	p.Pro590Ser	missense_variant	4/4	1	NM_001114133.3	ENSP00000378289.2
SYNPO2L	ENST00000372873.8	c.1096C>T	p.Pro366Ser	missense_variant	2/2	1		ENSP00000361964.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

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

Dec 11, 2023

The c.1768C>T (p.P590S) alteration is located in exon 4 (coding exon 4) of the SYNPO2L gene. This alteration results from a C to T substitution at nucleotide position 1768, causing the proline (P) at amino acid position 590 to be replaced by a serine (S). 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	Benign	0.072
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.3
DANN	Benign	0.83
DEOGEN2	Benign	0.0060	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.038	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.77	.;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.49	N;N
REVEL	Benign	0.0040
Sift	Benign	0.24	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0030	B;B
Vest4		0.023
MutPred		0.21		.;Gain of phosphorylation at P590 (P = 0.0043);
MVP		0.19
MPC		0.38
ClinPred		0.081	T
GERP RS		0.98
Varity_R		0.024
gMVP		0.39

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: chr10-75407642;