5-150617974-T-C

Position:

• chr5-150617974-T-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.-265-129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 167,402 control chromosomes in the GnomAD database, including 2,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (2010 hom., cov: 32)
  • Exomes 𝑓: 0.050 (89 hom.)
• Consequence: SYNPO ENST00000394243.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.527

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=-0.83).
• BP6: Variant 5-150617974-T-C is Benign according to our data. Variant chr5-150617974-T-C is described in ClinVar as [Benign]. Clinvar id is 1226601.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNPO	NM_001166208.2	c.-265-129T>C		intron_variant			NP_001159680.1
SYNPO	NM_001166209.2	c.-265-129T>C		intron_variant			NP_001159681.1
SYNPO	XM_006714755.4	c.-265-129T>C		intron_variant			XP_006714818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNPO	ENST00000394243.5	c.-265-129T>C		intron_variant		1		ENSP00000377789	A2
SYNPO	ENST00000522122.1	c.-265-129T>C		intron_variant		2		ENSP00000428378	A2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15977 AN: 152060 Hom.: 2001 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0392

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.0642

GnomAD4 exome AF: 0.0504 AC: 767 AN: 15224 Hom.: 89 AF XY: 0.0451 AC XY: 345 AN XY: 7654

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.0392

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.0410

Gnomad4 NFE exome AF: 0.0143

Gnomad4 OTH exome AF: 0.0613

GnomAD4 genome AF: 0.105 AC: 16017 AN: 152178 Hom.: 2010 Cov.: 32 AF XY: 0.107 AC XY: 7970 AN XY: 74398

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.0392

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.0273

Gnomad4 NFE AF: 0.0134

Gnomad4 OTH AF: 0.0659

Alfa AF: 0.0650 Hom.: 143

Bravo AF: 0.113

Asia WGS AF: 0.231 AC: 800 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	-0.83
CADD	Benign	6.5
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58237678; hg19: chr5-149997536;