rs306891

chrX-155754989-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304990.2(SPRY3):c.-281-12973G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,378 control chromosomes in the GnomAD database, including 10,465 homozygotes. There are 35,364 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (10465 hom., 35364 hem., cov: 31)
• Consequence: SPRY3 NM_001304990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPRY3	NM_001304990.2	c.-281-12973G>A		intron_variant		ENST00000695325.1
SPRY3	NM_001394353.1	c.-281-12973G>A		intron_variant
SPRY3	NM_001394354.1	c.-281-12973G>A		intron_variant
SPRY3	NM_001394355.1	c.-718-12973G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPRY3	ENST00000695325.1	c.-281-12973G>A		intron_variant			NM_001304990.2	P1
SPRY3	ENST00000675360.1	c.-281-12973G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57662 AN: 151262 Hom.: 10450 Cov.: 31 AF XY: 0.478 AC XY: 35317 AN XY: 73826

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.276

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.389

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.381 AC: 57720 AN: 151378 Hom.: 10465 Cov.: 31 AF XY: 0.478 AC XY: 35364 AN XY: 73952

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.394

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.4
Dann	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs306891; hg19: chrX-154984651;