dbSNP rs370701407: SPRED3:p.His51Gln (chr19-38390455-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001394336.1(SPRED3):c.153C>A(p.His51Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000091 in 1,098,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

SPRED3
NM_001394336.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.627

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRED3	NM_001394336.1 link	c.153C>A	p.His51Gln	missense_variant	Exon 2 of 6	ENST00000691638.1	NP_001381265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRED3	ENST00000691638.1 link	c.153C>A	p.His51Gln	missense_variant	Exon 2 of 6		NM_001394336.1	ENSP00000510478.1		Q2MJR0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.10e-7

AC:

AN:

1098892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

534368

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000109

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.68

D;.;D

Eigen

Benign

0.17

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.78

.;T;T

M_CAP

Uncertain

0.19

MetaRNN

Uncertain

0.54

D;D;D

MetaSVM

Uncertain

-0.11

MutationAssessor

Benign

1.3

L;.;L

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-4.5

.;.;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.029

.;.;D

Sift4G

Benign

0.18

T;T;T

Polyphen

0.91

P;.;P

Vest4

0.58

MutPred

0.50

Gain of MoRF binding (P = 0.0862);Gain of MoRF binding (P = 0.0862);Gain of MoRF binding (P = 0.0862);

MVP

0.85

MPC

0.93

ClinPred

0.97

GERP RS

3.0

Varity_R

0.43

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over