rs146345840

Positions:

• chr5-150649089-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_007286.6(SYNPO):​c.814C>T​(p.Pro272Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00661 in 1,613,852 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0068 (51 hom.)
• Consequence: SYNPO NM_007286.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.917

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043495297).
• BP6: Variant 5-150649089-C-T is Benign according to our data. Variant chr5-150649089-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 774 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNPO	NM_007286.6	c.814C>T	p.Pro272Ser	missense_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.814C>T	p.Pro272Ser	missense_variant	2/3	1	NM_007286.6	ENSP00000302139.4
SYNPO	ENST00000394243.5	c.1546C>T	p.Pro516Ser	missense_variant	3/3	1		ENSP00000377789.1
SYNPO	ENST00000519664.1	c.814C>T	p.Pro272Ser	missense_variant	2/2	1		ENSP00000429268.1
SYNPO	ENST00000522122.1	c.1546C>T	p.Pro516Ser	missense_variant	3/3	2		ENSP00000428378.1

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 774 AN: 152172 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00789

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00485 AC: 1211 AN: 249610 Hom.: 5 AF XY: 0.00466 AC XY: 630 AN XY: 135312

Gnomad AFR exome AF: 0.00120

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.0105

Gnomad NFE exome AF: 0.00783

Gnomad OTH exome AF: 0.00558

GnomAD4 exome AF: 0.00677 AC: 9895 AN: 1461562 Hom.: 51 Cov.: 32 AF XY: 0.00653 AC XY: 4749 AN XY: 727042

Gnomad4 AFR exome AF: 0.000986

Gnomad4 AMR exome AF: 0.00145

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00940

Gnomad4 NFE exome AF: 0.00806

Gnomad4 OTH exome AF: 0.00520

GnomAD4 genome AF: 0.00508 AC: 774 AN: 152290 Hom.: 5 Cov.: 33 AF XY: 0.00540 AC XY: 402 AN XY: 74470

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.00789

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00669 Hom.: 4

Bravo AF: 0.00431

TwinsUK AF: 0.00836 AC: 31

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00663 AC: 57

ExAC AF: 0.00474 AC: 576

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00654

EpiControl AF: 0.00806

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 07, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	SYNPO: BP4, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 15, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.18
DANN	Benign	0.78
DEOGEN2	Benign	0.20	T;T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.70	.;T;T;T
MetaRNN	Benign	0.0043	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.088	T;T;T;T
Sift4G	Benign	0.27	T;T;T;T
Polyphen		0.0090	B;B;B;.
Vest4		0.080
MVP		0.30
MPC		0.36
ClinPred		0.0054	T
GERP RS		-1.7
Varity_R		0.033
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs146345840; hg19: chr5-150028651;