5-150618349-G-A

Position:

• chr5-150618349-G-A

Variant summary

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

The NM_001166208.2(SYNPO):​c.-19G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,532,838 control chromosomes in the GnomAD database, including 649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (178 hom., cov: 33)
  • Exomes 𝑓: 0.0082 (471 hom.)
• Consequence: SYNPO NM_001166208.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.43

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 (BayesDel_noAF=-0.94).
• BP6: Variant 5-150618349-G-A is Benign according to our data. Variant chr5-150618349-G-A is described in ClinVar as [Benign]. Clinvar id is 1236697.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNPO	NM_001166208.2	c.-19G>A		5_prime_UTR_variant	2/3		NP_001159680.1
SYNPO	NM_001166209.2	c.-19G>A		5_prime_UTR_variant	2/3		NP_001159681.1
SYNPO	XM_006714755.4	c.-19G>A		5_prime_UTR_variant	2/4		XP_006714818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNPO	ENST00000394243.5	c.-19G>A		5_prime_UTR_variant	2/3	1		ENSP00000377789.1
SYNPO	ENST00000522122.1	c.-19G>A		5_prime_UTR_variant	2/3	2		ENSP00000428378.1

Frequencies

GnomAD3 genomes AF: 0.0285 AC: 4314 AN: 151382 Hom.: 175 Cov.: 33

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00762

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0149

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.00180

Gnomad MID AF: 0.00671

Gnomad NFE AF: 0.000796

Gnomad OTH AF: 0.0174

GnomAD3 exomes AF: 0.0190 AC: 2812 AN: 147782 Hom.: 107 AF XY: 0.0222 AC XY: 1748 AN XY: 78580

Gnomad AFR exome AF: 0.0839

Gnomad AMR exome AF: 0.00491

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0114

Gnomad SAS exome AF: 0.0839

Gnomad FIN exome AF: 0.00206

Gnomad NFE exome AF: 0.000585

Gnomad OTH exome AF: 0.0123

GnomAD4 exome AF: 0.00815 AC: 11260 AN: 1381332 Hom.: 471 Cov.: 31 AF XY: 0.0102 AC XY: 6927 AN XY: 680028

Gnomad4 AFR exome AF: 0.0908

Gnomad4 AMR exome AF: 0.00525

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00863

Gnomad4 SAS exome AF: 0.0835

Gnomad4 FIN exome AF: 0.00172

Gnomad4 NFE exome AF: 0.000558

Gnomad4 OTH exome AF: 0.0130

GnomAD4 genome AF: 0.0285 AC: 4324 AN: 151506 Hom.: 178 Cov.: 33 AF XY: 0.0289 AC XY: 2138 AN XY: 74032

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.00761

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.0881

Gnomad4 FIN AF: 0.00180

Gnomad4 NFE AF: 0.000796

Gnomad4 OTH AF: 0.0172

Alfa AF: 0.0167 Hom.: 27

Bravo AF: 0.0299

Asia WGS AF: 0.0650 AC: 225 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
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.017
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6579796; hg19: chr5-149997911;