19-38392141-T-G

Variant names:

• chr19-38392141-T-G
• rs12609878
• NM_001394336.1:c.346+27T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394336.1. 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
	SPRED3	NM_001394336.1	MANE Select	c.346+27T>G		intron	N/A	NP_001381265.1	Q2MJR0-1
	SPRED3	NM_001042522.3		c.346+27T>G		intron	N/A	NP_001035987.1	Q2MJR0-1
	SPRED3	NM_001394337.1		c.346+27T>G		intron	N/A	NP_001381266.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED3	ENST00000691638.1	MANE Select	c.346+27T>G		intron	N/A	ENSP00000510478.1	Q2MJR0-1
	SPRED3	ENST00000338502.8	TSL:1	c.346+27T>G		intron	N/A	ENSP00000345405.4	Q2MJR0-1
	SPRED3	ENST00000587564.2	TSL:1	n.350+27T>G		intron	N/A

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

GnomAD2 exomes AF: 0.189 AC: 46960 AN: 248744 AF XY: 0.182

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 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

African (AFR) AF: 0.231 AC: 7718 AN: 33456

American (AMR) AF: 0.285 AC: 12742 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 4028 AN: 26102

East Asian (EAS) AF: 0.521 AC: 20682 AN: 39662

South Asian (SAS) AF: 0.196 AC: 16873 AN: 86234

European-Finnish (FIN) AF: 0.116 AC: 6173 AN: 53330

Middle Eastern (MID) AF: 0.155 AC: 890 AN: 5738

European-Non Finnish (NFE) AF: 0.124 AC: 137847 AN: 1109956

Other (OTH) AF: 0.165 AC: 9937 AN: 60274

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

African (AFR) AF: 0.231 AC: 9589 AN: 41452

American (AMR) AF: 0.238 AC: 3642 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3466

East Asian (EAS) AF: 0.524 AC: 2704 AN: 5158

South Asian (SAS) AF: 0.206 AC: 990 AN: 4814

European-Finnish (FIN) AF: 0.114 AC: 1213 AN: 10610

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7961 AN: 67974

Other (OTH) AF: 0.178 AC: 375 AN: 2110

Alfa AF: 0.142 Hom.: 3985

Bravo AF: 0.191

Asia WGS AF: 0.338 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.60
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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