chr19-38392141-T-G

Position:

• chr19-38392141-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394336.1(SPRED3):​c.346+27T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,611,504 control chromosomes in the GnomAD database, including 23,405 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (3049 hom., cov: 31)
  • Exomes 𝑓: 0.15 (20356 hom.)
• Consequence: SPRED3 NM_001394336.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

Genes affected

SPRED3 (HGNC:31041): (sprouty related EVH1 domain containing 3) This gene encodes a protein with a C-terminal Sprouty-like cysteine-rich domain (SRY) and an N-terminal Ena/Vasodilator-stimulated phosphoprotein (VASP) homology-1 (EVH-1) domain. The encoded protein is a member of a family of proteins that negatively regulates mitogen-activated protein (MAP) kinase signaling, particularly during organogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

SPRED3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRED3	NM_001394336.1	c.346+27T>G		intron_variant		ENST00000691638.1	NP_001381265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRED3	ENST00000691638.1	c.346+27T>G		intron_variant			NM_001394336.1	ENSP00000510478.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27034 AN: 151946 Hom.: 3049 Cov.: 31

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.176

GnomAD3 exomes AF: 0.189 AC: 46960 AN: 248744 Hom.: 6097 AF XY: 0.182 AC XY: 24509 AN XY: 134936

Gnomad AFR exome AF: 0.226

Gnomad AMR exome AF: 0.290

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.519

Gnomad SAS exome AF: 0.197

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.149 AC: 216890 AN: 1459440 Hom.: 20356 Cov.: 32 AF XY: 0.149 AC XY: 107852 AN XY: 725492

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.521

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.178 AC: 27084 AN: 152064 Hom.: 3049 Cov.: 31 AF XY: 0.183 AC XY: 13591 AN XY: 74346

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.178

Alfa AF: 0.135 Hom.: 2370

Bravo AF: 0.191

Asia WGS AF: 0.338 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs12609878; hg19: chr19-38882781; COSMIC: COSV58314335; COSMIC: COSV58314335;