19-38394761-C-G

Variant names:

• chr19-38394761-C-G
• rs566483883
• NM_001394336.1:c.542C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001394336.1(SPRED3):​c.542C>G​(p.Pro181Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000431 in 1,576,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P181H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: SPRED3 NM_001394336.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.98
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15617728).

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.542C>G	p.Pro181Arg	missense	Exon 5 of 6	NP_001381265.1	Q2MJR0-1
	SPRED3	NM_001042522.3		c.542C>G	p.Pro181Arg	missense	Exon 4 of 5	NP_001035987.1	Q2MJR0-1
	SPRED3	NM_001394338.1		c.38C>G	p.Pro13Arg	missense	Exon 4 of 5	NP_001381267.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED3	ENST00000691638.1	MANE Select	c.542C>G	p.Pro181Arg	missense	Exon 5 of 6	ENSP00000510478.1	Q2MJR0-1
	SPRED3	ENST00000338502.8	TSL:1	c.542C>G	p.Pro181Arg	missense	Exon 4 of 5	ENSP00000345405.4	Q2MJR0-1
	SPRED3	ENST00000587013.6	TSL:5	c.674C>G	p.Pro225Arg	missense	Exon 4 of 5	ENSP00000467540.1	K7EPU5

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152238 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000666 AC: 12 AN: 180212 AF XY: 0.0000606

Gnomad AFR exome AF: 0.000503

Gnomad AMR exome AF: 0.0000362

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000140

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000281 AC: 40 AN: 1423652 Hom.: 0 Cov.: 31 AF XY: 0.0000213 AC XY: 15 AN XY: 704996

African (AFR) AF: 0.000392 AC: 13 AN: 33128

American (AMR) AF: 0.0000256 AC: 1 AN: 39036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25350

East Asian (EAS) AF: 0.000415 AC: 16 AN: 38538

South Asian (SAS) AF: 0.0000734 AC: 6 AN: 81758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1096458

Other (OTH) AF: 0.0000339 AC: 2 AN: 59020

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152356 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74502

African (AFR) AF: 0.000649 AC: 27 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000200

ExAC AF: 0.0000768 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.077
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.76	N
PhyloP100		4.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.23
Sift	Benign	0.46	T
Sift4G	Benign	0.061	T
Polyphen		0.91	P
Vest4		0.65
MVP		0.86
MPC		0.35
ClinPred		0.066	T
GERP RS		3.0
Varity_R		0.057
gMVP		0.49
Mutation Taster		=68/32	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

Other links and lift over

dbSNP: rs566483883; hg19: chr19-38885401;