rs779201129

Variant names:

• chrX-155773926-C-A
• rs779201129
• NM_001304990.2:c.55C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-155773926-C-A
• chrX-155773926-C-G
• chrX-155773926-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001304990.2(SPRY3):​c.55C>A​(p.Arg19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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. R19C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SPRY3 NM_001304990.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 0 publications found

Genes affected

SPRY3 (HGNC:11271): (sprouty RTK signaling antagonist 3) Involved in negative regulation of MAPK cascade. Predicted to be located in membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40872896).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304990.2. 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
	SPRY3	NM_001304990.2	MANE Select	c.55C>A	p.Arg19Ser	missense	Exon 3 of 3	NP_001291919.1	O43610
	SPRY3	NM_001394353.1		c.55C>A	p.Arg19Ser	missense	Exon 4 of 4	NP_001381282.1	O43610
	SPRY3	NM_001394354.1		c.55C>A	p.Arg19Ser	missense	Exon 4 of 4	NP_001381283.1	O43610

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRY3	ENST00000695325.1	MANE Select	c.55C>A	p.Arg19Ser	missense	Exon 3 of 3	ENSP00000511806.1	O43610
	SPRY3	ENST00000302805.7	TSL:1	c.55C>A	p.Arg19Ser	missense	Exon 2 of 2	ENSP00000302978.2	O43610
	SPRY3	ENST00000675360.1		c.55C>A	p.Arg19Ser	missense	Exon 4 of 4	ENSP00000502489.1	O43610

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.39	B
Vest4		0.47
MutPred		0.53		Gain of disorder (P = 0.055)
MVP		1.0
MPC		0.25
ClinPred		0.95	D
GERP RS		2.3
Varity_R		0.59
Mutation Taster		=83/17	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: rs779201129; hg19: chrX-155003588;