rs148367718

Variant names:

• chr10-73647263-G-A
• rs148367718
• NM_001114133.3:c.2389C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-73647263-G-A
• chr10-73647263-G-C
• chr10-73647263-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001114133.3(SYNPO2L):​c.2389C>T​(p.Pro797Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P797T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: SYNPO2L NM_001114133.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029407233).

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.2389C>T	p.Pro797Ser	missense	Exon 4 of 4	NP_001107605.1	Q9H987-1
	SYNPO2L	NM_024875.5		c.1717C>T	p.Pro573Ser	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.2389C>T	p.Pro797Ser	missense	Exon 4 of 4	ENSP00000378289.2	Q9H987-1
	SYNPO2L	ENST00000372873.8	TSL:1	c.1717C>T	p.Pro573Ser	missense	Exon 2 of 2	ENSP00000361964.4	Q9H987-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152086 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251412 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000192 AC: 28 AN: 1461884 Hom.: 0 Cov.: 37 AF XY: 0.0000124 AC XY: 9 AN XY: 727244

African (AFR) AF: 0.000388 AC: 13 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

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

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

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112002

Other (OTH) AF: 0.0000993 AC: 6 AN: 60396

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152086 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74302

African (AFR) AF: 0.0000242 AC: 1 AN: 41376

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.19
DANN	Benign	0.81
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.53	N
PhyloP100		-0.52
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.032
Sift	Benign	0.61	T
Sift4G	Benign	0.78	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.20		Gain of phosphorylation at P797 (P = 0.0191)
MVP		0.16
MPC		0.38
ClinPred		0.026	T
GERP RS		0.69
Varity_R		0.029
gMVP		0.22
Mutation Taster		=97/3	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: rs148367718; hg19: chr10-75407021; COSMIC: COSV100866407;