rs146345840

Variant names:

• chr5-150649089-C-T
• rs146345840
• NM_007286.6:c.814C>T
• SYNPO p.Pro272Ser

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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
• Publications: 11 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 -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 Benign/Likely_benign. ClinVar VariationId is 445853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 774 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007286.6. 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_007286.6	MANE Select	c.814C>T	p.Pro272Ser	missense	Exon 2 of 3	NP_009217.3
	SYNPO	NM_001166208.2		c.1546C>T	p.Pro516Ser	missense	Exon 3 of 3	NP_001159680.1	Q8N3V7-1
	SYNPO	NM_001166209.2		c.1546C>T	p.Pro516Ser	missense	Exon 3 of 3	NP_001159681.1	Q8N3V7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO	ENST00000307662.5	TSL:1 MANE Select	c.814C>T	p.Pro272Ser	missense	Exon 2 of 3	ENSP00000302139.4	Q8N3V7-2
	SYNPO	ENST00000394243.5	TSL:1	c.1546C>T	p.Pro516Ser	missense	Exon 3 of 3	ENSP00000377789.1	Q8N3V7-1
	SYNPO	ENST00000519664.1	TSL:1	c.814C>T	p.Pro272Ser	missense	Exon 2 of 2	ENSP00000429268.1	Q8N3V7-3

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

GnomAD2 exomes AF: 0.00485 AC: 1211 AN: 249610 AF XY: 0.00466

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 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

African (AFR) AF: 0.000986 AC: 33 AN: 33462

American (AMR) AF: 0.00145 AC: 65 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86246

European-Finnish (FIN) AF: 0.00940 AC: 502 AN: 53396

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.00806 AC: 8961 AN: 1111800

Other (OTH) AF: 0.00520 AC: 314 AN: 60372

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

African (AFR) AF: 0.00142 AC: 59 AN: 41558

American (AMR) AF: 0.00216 AC: 33 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0124 AC: 132 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00789 AC: 537 AN: 68024

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00615 Hom.: 4

Bravo AF: 0.00431

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00654

EpiControl AF: 0.00806

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.92
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.13
Sift	Benign	0.088	T
Sift4G	Benign	0.27	T
Varity_R		0.033
gMVP		0.31
Mutation Taster		=99/1	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

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

Other links and lift over

dbSNP: rs146345840;

hg19: chr5-150028651;