X-155754989-G-A

Variant names:

• chrX-155754989-G-A
• rs306891
• NM_001304990.2:c.-281-12973G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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]

ENSG00000298691 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPRY3	NM_001304990.2	c.-281-12973G>A		intron_variant	Intron 1 of 2	ENST00000695325.1	NP_001291919.1
SPRY3	NM_001394353.1	c.-281-12973G>A		intron_variant	Intron 2 of 3		NP_001381282.1
SPRY3	NM_001394354.1	c.-281-12973G>A		intron_variant	Intron 2 of 3		NP_001381283.1
SPRY3	NM_001394355.1	c.-718-12973G>A		intron_variant	Intron 1 of 3		NP_001381284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRY3	ENST00000695325.1	c.-281-12973G>A		intron_variant	Intron 1 of 2		NM_001304990.2	ENSP00000511806.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57662 AN: 151262 Hom.: 10450 Cov.: 31

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

African (AFR) AF: 0.317 AC: 13082 AN: 41264

American (AMR) AF: 0.459 AC: 6974 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1106 AN: 3460

East Asian (EAS) AF: 0.485 AC: 2493 AN: 5136

South Asian (SAS) AF: 0.520 AC: 2497 AN: 4802

European-Finnish (FIN) AF: 0.506 AC: 5312 AN: 10502

Middle Eastern (MID) AF: 0.279 AC: 81 AN: 290

European-Non Finnish (NFE) AF: 0.368 AC: 24938 AN: 67724

Other (OTH) AF: 0.394 AC: 825 AN: 2096

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
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs306891; hg19: chrX-154984651;