NM_001304990.2:c.55C>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001304990.2(SPRY3):​c.55C>G​(p.Arg19Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom. 0 hem.)
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>G	p.Arg19Gly	missense	Exon 3 of 3	NP_001291919.1	O43610
	SPRY3	NM_001394353.1		c.55C>G	p.Arg19Gly	missense	Exon 4 of 4	NP_001381282.1	O43610
	SPRY3	NM_001394354.1		c.55C>G	p.Arg19Gly	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>G	p.Arg19Gly	missense	Exon 3 of 3	ENSP00000511806.1	O43610
	SPRY3	ENST00000302805.7	TSL:1	c.55C>G	p.Arg19Gly	missense	Exon 2 of 2	ENSP00000302978.2	O43610
	SPRY3	ENST00000675360.1		c.55C>G	p.Arg19Gly	missense	Exon 4 of 4	ENSP00000502489.1	O43610

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461648 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727136

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111830

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.56	P
Vest4		0.55
MutPred		0.54		Loss of stability (P = 0.0342)
MVP		1.0
MPC		0.34
ClinPred		0.93	D
GERP RS		2.3
Varity_R		0.54
Mutation Taster		=80/20	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;