Genetic Variant SPRED3:p.Gly25Val (chr19-38390376-G-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001394336.1(SPRED3):c.74G>T(p.Gly25Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,240,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

SPRED3
NM_001394336.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.90

Publications

0 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.892

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPRED3	NM_001394336.1	MANE Select	c.74G>T	p.Gly25Val	missense	Exon 2 of 6	NP_001381265.1	Q2MJR0-1
SPRED3	NM_001042522.3		c.74G>T	p.Gly25Val	missense	Exon 1 of 5	NP_001035987.1	Q2MJR0-1
SPRED3	NM_001394337.1		c.74G>T	p.Gly25Val	missense	Exon 2 of 5	NP_001381266.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPRED3	ENST00000691638.1	MANE Select	c.74G>T	p.Gly25Val	missense	Exon 2 of 6	ENSP00000510478.1	Q2MJR0-1
SPRED3	ENST00000338502.8	TSL:1	c.74G>T	p.Gly25Val	missense	Exon 1 of 5	ENSP00000345405.4	Q2MJR0-1
SPRED3	ENST00000587564.2	TSL:1	n.78G>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000852

AC:

AN:

117326

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000161

AC:

AN:

1240070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

602044

show subpopulations

African (AFR)

AF:

0.0000394

AC:

AN:

25396

American (AMR)

AF:

0.00

AC:

AN:

17768

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17206

East Asian (EAS)

AF:

0.00

AC:

AN:

30816

South Asian (SAS)

AF:

0.0000210

AC:

AN:

47554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4824

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

999774

Other (OTH)

AF:

0.00

AC:

AN:

50184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000835

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.31

MetaRNN

Pathogenic

0.89

MetaSVM

Uncertain

0.75

MutationAssessor

Uncertain

2.6

PhyloP100

9.9

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-7.8

REVEL

Pathogenic

0.85

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.84

MutPred

0.65

Loss of sheet (P = 0.0181)

MVP

0.97

MPC

1.0

ClinPred

0.96

GERP RS

4.0

PromoterAI

-0.056

Neutral

(source)

Varity_R

0.88

gMVP

0.68

Mutation Taster

=18/82

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over