chr19-38392094-C-A

Variant names:

• chr19-38392094-C-A
• rs748612215
• NM_001394336.1:c.326C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001394336.1(SPRED3):​c.326C>A​(p.Ala109Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A109V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SPRED3 NM_001394336.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.42
• Publications: 1 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: 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, 0.87

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.326C>A	p.Ala109Glu	missense	Exon 3 of 6	NP_001381265.1	Q2MJR0-1
	SPRED3	NM_001042522.3		c.326C>A	p.Ala109Glu	missense	Exon 2 of 5	NP_001035987.1	Q2MJR0-1
	SPRED3	NM_001394337.1		c.326C>A	p.Ala109Glu	missense	Exon 3 of 5	NP_001381266.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED3	ENST00000691638.1	MANE Select	c.326C>A	p.Ala109Glu	missense	Exon 3 of 6	ENSP00000510478.1	Q2MJR0-1
	SPRED3	ENST00000338502.8	TSL:1	c.326C>A	p.Ala109Glu	missense	Exon 2 of 5	ENSP00000345405.4	Q2MJR0-1
	SPRED3	ENST00000587564.2	TSL:1	n.330C>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.40	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.062	T
Polyphen		0.99	D
Vest4		0.66
MutPred		0.70		Gain of relative solvent accessibility (P = 0.1259)
MVP		0.94
MPC		1.0
ClinPred		1.0	D
GERP RS		3.6
Varity_R		0.77
gMVP		0.92
Mutation Taster		=76/24	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: rs748612215; hg19: chr19-38882734;