10-73647175-C-G

Variant names:

• chr10-73647175-C-G
• rs769605168
• NM_001114133.3:c.2477G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001114133.3(SYNPO2L):​c.2477G>C​(p.Arg826Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SYNPO2L NM_001114133.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114133.3. 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
	SYNPO2L	NM_001114133.3	MANE Select	c.2477G>C	p.Arg826Pro	missense	Exon 4 of 4	NP_001107605.1	Q9H987-1
	SYNPO2L	NM_024875.5		c.1805G>C	p.Arg602Pro	missense	Exon 2 of 2	NP_079151.2	Q9H987-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO2L	ENST00000394810.3	TSL:1 MANE Select	c.2477G>C	p.Arg826Pro	missense	Exon 4 of 4	ENSP00000378289.2	Q9H987-1
	SYNPO2L	ENST00000372873.8	TSL:1	c.1805G>C	p.Arg602Pro	missense	Exon 2 of 2	ENSP00000361964.4	Q9H987-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461724 Hom.: 0 Cov.: 37 AF XY: 0.00000550 AC XY: 4 AN XY: 727150

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111892

Other (OTH) AF: 0.0000166 AC: 1 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	0.0099	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0089	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.099
Sift	Uncertain	0.021	D
Sift4G	Benign	0.28	T
Polyphen		1.0	D
Vest4		0.49
MutPred		0.30		Loss of MoRF binding (P = 0.015)
MVP		0.73
MPC		1.4
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.55
gMVP		0.49
Mutation Taster		=87/13	polymorphism

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: rs769605168; hg19: chr10-75406933;