rs6579797

chr5-150618566-G-Achr5-150618566-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000394243.5(SYNPO):c.199G>A(p.Asp67Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 1,550,392 control chromosomes in the GnomAD database, including 5,354 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.094 (1577 hom., cov: 32)
  • Exomes 𝑓: 0.036 (3777 hom.)
• Consequence: SYNPO ENST00000394243.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.11

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036984086).
• BP6: Variant 5-150618566-G-A is Benign according to our data. Variant chr5-150618566-G-A is described in ClinVar as [Benign]. Clinvar id is 1283897.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNPO	NM_001166208.2	c.199G>A	p.Asp67Asn	missense_variant	2/3
SYNPO	NM_001166209.2	c.199G>A	p.Asp67Asn	missense_variant	2/3
SYNPO	XM_006714755.4	c.199G>A	p.Asp67Asn	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNPO	ENST00000394243.5	c.199G>A	p.Asp67Asn	missense_variant	2/3	1		A2
SYNPO	ENST00000522122.1	c.199G>A	p.Asp67Asn	missense_variant	2/3	2		A2

Frequencies

GnomAD3 genomes AF: 0.0935 AC: 14224 AN: 152072 Hom.: 1569 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0350

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.0275

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0561

GnomAD3 exomes AF: 0.0671 AC: 10300 AN: 153396 Hom.: 969 AF XY: 0.0698 AC XY: 5684 AN XY: 81414

Gnomad AFR exome AF: 0.251

Gnomad AMR exome AF: 0.0212

Gnomad ASJ exome AF: 0.00154

Gnomad EAS exome AF: 0.265

Gnomad SAS exome AF: 0.152

Gnomad FIN exome AF: 0.0307

Gnomad NFE exome AF: 0.0133

Gnomad OTH exome AF: 0.0424

GnomAD4 exome AF: 0.0363 AC: 50747 AN: 1398202 Hom.: 3777 Cov.: 32 AF XY: 0.0386 AC XY: 26601 AN XY: 689418

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.0234

Gnomad4 ASJ exome AF: 0.00151

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.0300

Gnomad4 NFE exome AF: 0.0144

Gnomad4 OTH exome AF: 0.0524

GnomAD4 genome AF: 0.0937 AC: 14257 AN: 152190 Hom.: 1577 Cov.: 32 AF XY: 0.0959 AC XY: 7139 AN XY: 74408

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.0275

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.0579

Alfa AF: 0.0243 Hom.: 51

Bravo AF: 0.100

TwinsUK AF: 0.0135 AC: 50

ALSPAC AF: 0.0138 AC: 53

ESP6500AA AF: 0.235 AC: 325

ESP6500EA AF: 0.0129 AC: 41

ExAC AF: 0.0804 AC: 2116

Asia WGS AF: 0.228 AC: 789 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	6.3
Dann	Benign	0.77
DEOGEN2	Benign	0.054	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00054	N
MetaRNN	Benign	0.0037	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.1	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.59	N;N
REVEL	Benign	0.10
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.0050
MPC		0.34
ClinPred		0.0014	T
GERP RS		3.6
Varity_R		0.033
gMVP		0.029

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6579797; hg19: chr5-149998128; COSMIC: COSV67783267; COSMIC: COSV67783267;