NM_001394336.1:c.548G>T

Variant names:

• chr19-38394767-G-T
• rs865940339
• NM_001394336.1:c.548G>T

Variant summary

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

The NM_001394336.1(SPRED3):​c.548G>T​(p.Arg183Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000914 in 1,422,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: SPRED3 NM_001394336.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.451
• Publications: 3 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=0.12926105).

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.548G>T	p.Arg183Leu	missense	Exon 5 of 6	NP_001381265.1	Q2MJR0-1
	SPRED3	NM_001042522.3		c.548G>T	p.Arg183Leu	missense	Exon 4 of 5	NP_001035987.1	Q2MJR0-1
	SPRED3	NM_001394338.1		c.44G>T	p.Arg15Leu	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.548G>T	p.Arg183Leu	missense	Exon 5 of 6	ENSP00000510478.1	Q2MJR0-1
	SPRED3	ENST00000338502.8	TSL:1	c.548G>T	p.Arg183Leu	missense	Exon 4 of 5	ENSP00000345405.4	Q2MJR0-1
	SPRED3	ENST00000587013.6	TSL:5	c.680G>T	p.Arg227Leu	missense	Exon 4 of 5	ENSP00000467540.1	K7EPU5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000112 AC: 2 AN: 178812 AF XY: 0.0000204

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000141

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000914 AC: 13 AN: 1422382 Hom.: 0 Cov.: 31 AF XY: 0.0000114 AC XY: 8 AN XY: 704360

African (AFR) AF: 0.0000604 AC: 2 AN: 33110

American (AMR) AF: 0.00 AC: 0 AN: 38952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25330

East Asian (EAS) AF: 0.000260 AC: 10 AN: 38508

South Asian (SAS) AF: 0.00 AC: 0 AN: 81614

European-Finnish (FIN) AF: 0.0000225 AC: 1 AN: 44416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5522

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095932

Other (OTH) AF: 0.00 AC: 0 AN: 58998

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.10
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.45
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.16
Sift	Benign	0.61	T
Sift4G	Benign	0.32	T
Polyphen		0.39	B
Vest4		0.41
MutPred		0.20		Loss of glycosylation at P181 (P = 0.0672)
MVP		0.78
MPC		0.32
ClinPred		0.12	T
GERP RS		0.82
Varity_R		0.15
gMVP		0.46
Mutation Taster		=86/14	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: rs865940339; hg19: chr19-38885407;