chr19-38394772-C-A

Variant names:

• chr19-38394772-C-A
• rs112201791
• NM_001394336.1:c.553C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001394336.1(SPRED3):​c.553C>A​(p.Arg185Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,571,178 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign 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. R185C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (9 hom.)
• Consequence: SPRED3 NM_001394336.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006659776).
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

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.553C>A	p.Arg185Ser	missense	Exon 5 of 6	NP_001381265.1	Q2MJR0-1
	SPRED3	NM_001042522.3		c.553C>A	p.Arg185Ser	missense	Exon 4 of 5	NP_001035987.1	Q2MJR0-1
	SPRED3	NM_001394338.1		c.49C>A	p.Arg17Ser	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.553C>A	p.Arg185Ser	missense	Exon 5 of 6	ENSP00000510478.1	Q2MJR0-1
	SPRED3	ENST00000338502.8	TSL:1	c.553C>A	p.Arg185Ser	missense	Exon 4 of 5	ENSP00000345405.4	Q2MJR0-1
	SPRED3	ENST00000587013.6	TSL:5	c.685C>A	p.Arg229Ser	missense	Exon 4 of 5	ENSP00000467540.1	K7EPU5

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 182 AN: 152254 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00116 AC: 203 AN: 174684 AF XY: 0.000981

Gnomad AFR exome AF: 0.000102

Gnomad AMR exome AF: 0.00196

Gnomad ASJ exome AF: 0.000712

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00186

Gnomad OTH exome AF: 0.000871

GnomAD4 exome AF: 0.00208 AC: 2955 AN: 1418806 Hom.: 9 Cov.: 31 AF XY: 0.00207 AC XY: 1454 AN XY: 702232

African (AFR) AF: 0.000242 AC: 8 AN: 33072

American (AMR) AF: 0.00190 AC: 73 AN: 38468

Ashkenazi Jewish (ASJ) AF: 0.000594 AC: 15 AN: 25262

East Asian (EAS) AF: 0.0000260 AC: 1 AN: 38444

South Asian (SAS) AF: 0.00 AC: 0 AN: 81280

European-Finnish (FIN) AF: 0.000114 AC: 5 AN: 43872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5456

European-Non Finnish (NFE) AF: 0.00249 AC: 2727 AN: 1094058

Other (OTH) AF: 0.00214 AC: 126 AN: 58894

GnomAD4 genome AF: 0.00120 AC: 183 AN: 152372 Hom.: 0 Cov.: 32 AF XY: 0.00113 AC XY: 84 AN XY: 74516

African (AFR) AF: 0.000313 AC: 13 AN: 41590

American (AMR) AF: 0.00170 AC: 26 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

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: 0.00195 AC: 133 AN: 68042

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00116 Hom.: 0

Bravo AF: 0.00143

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000791 AC: 3

ESP6500EA AF: 0.00138 AC: 11

ExAC AF: 0.000701 AC: 82

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.0067	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.35
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.16
Sift	Benign	0.89	T
Sift4G	Benign	0.83	T
Polyphen		0.26	B
Vest4		0.32
MVP		0.62
MPC		0.29
ClinPred		0.017	T
GERP RS		-0.71
Varity_R		0.11
gMVP		0.53
Mutation Taster		=95/5	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: rs112201791; hg19: chr19-38885412;