ENST00000394243.5:c.199G>C

Variant names:

• chr5-150618566-G-C
• rs6579797
• ENST00000394243.5:c.199G>C
• SYNPO p.Asp67His

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000394243.5(SYNPO):​c.199G>C​(p.Asp67His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000987 in 1,550,418 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. D67N) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000058 (1 hom.)
• Consequence: SYNPO ENST00000394243.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048027635).
• BS2: High AC in GnomAd4 at 72 AD gene.

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>C	p.Asp67His	missense	Exon 2 of 3	NP_001159680.1	Q8N3V7-1
	SYNPO	NM_001166209.2		c.199G>C	p.Asp67His	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>C	p.Asp67His	missense	Exon 2 of 3	ENSP00000377789.1	Q8N3V7-1
	SYNPO	ENST00000522122.1	TSL:2	c.199G>C	p.Asp67His	missense	Exon 2 of 3	ENSP00000428378.1	Q8N3V7-1

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152088 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000130 AC: 20 AN: 153396 AF XY: 0.0000614

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.0000406

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: 0.00

GnomAD4 exome AF: 0.0000579 AC: 81 AN: 1398212 Hom.: 1 Cov.: 32 AF XY: 0.0000551 AC XY: 38 AN XY: 689424

African (AFR) AF: 0.00222 AC: 70 AN: 31572

American (AMR) AF: 0.000140 AC: 5 AN: 35682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25150

East Asian (EAS) AF: 0.00 AC: 0 AN: 35702

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078204

Other (OTH) AF: 0.0000863 AC: 5 AN: 57922

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32 AN XY: 74418

African (AFR) AF: 0.00169 AC: 70 AN: 41504

American (AMR) AF: 0.000131 AC: 2 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000260 Hom.: 83

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Uncertain	0.98
DEOGEN2	Benign	0.070	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.040
Sift	Uncertain	0.016	D
Sift4G	Benign	0.13	T
Varity_R		0.062
gMVP		0.079
Mutation Taster		=99/1	polymorphism

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;