ENST00000394243.5:c.199G>A

Variant names:

• chr5-150618566-G-A
• rs6579797
• ENST00000394243.5:c.199G>A
• SYNPO p.Asp67Asn

Variant summary

Our verdict is Benign. The variant received -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. 14/20 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
• Publications: 8 publications found

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]

SYNPO Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394243.5. 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
	SYNPO	NM_001166208.2		c.199G>A	p.Asp67Asn	missense	Exon 2 of 3	NP_001159680.1	Q8N3V7-1
	SYNPO	NM_001166209.2		c.199G>A	p.Asp67Asn	missense	Exon 2 of 3	NP_001159681.1	Q8N3V7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO	ENST00000394243.5	TSL:1	c.199G>A	p.Asp67Asn	missense	Exon 2 of 3	ENSP00000377789.1	Q8N3V7-1
	SYNPO	ENST00000522122.1	TSL:2	c.199G>A	p.Asp67Asn	missense	Exon 2 of 3	ENSP00000428378.1	Q8N3V7-1

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

GnomAD2 exomes AF: 0.0671 AC: 10300 AN: 153396 AF XY: 0.0698

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 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

African (AFR) AF: 0.250 AC: 7884 AN: 31572

American (AMR) AF: 0.0234 AC: 834 AN: 35682

Ashkenazi Jewish (ASJ) AF: 0.00151 AC: 38 AN: 25150

East Asian (EAS) AF: 0.281 AC: 10025 AN: 35702

South Asian (SAS) AF: 0.148 AC: 11738 AN: 79210

European-Finnish (FIN) AF: 0.0300 AC: 1473 AN: 49100

Middle Eastern (MID) AF: 0.0317 AC: 180 AN: 5670

European-Non Finnish (NFE) AF: 0.0144 AC: 15539 AN: 1078194

Other (OTH) AF: 0.0524 AC: 3036 AN: 57922

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

African (AFR) AF: 0.245 AC: 10157 AN: 41492

American (AMR) AF: 0.0348 AC: 533 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1382 AN: 5170

South Asian (SAS) AF: 0.170 AC: 819 AN: 4822

European-Finnish (FIN) AF: 0.0275 AC: 292 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 944 AN: 68004

Other (OTH) AF: 0.0579 AC: 122 AN: 2108

Alfa AF: 0.0342 Hom.: 83

Bravo AF: 0.100

Asia WGS AF: 0.228 AC: 789 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00054	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.1	N
PhyloP100		1.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.033
gMVP		0.029
Mutation Taster		=98/2	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6579797;

hg19: chr5-149998128;

COSMIC: COSV67783267;

COSMIC: COSV67783267;