Genetic Variant SPRY3:p.Lys36Lys (chrX-155773979-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3BP6_ModerateBS2

The NM_001304990.2(SPRY3):c.108A>G(p.Lys36Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000333 in 1,613,942 control chromosomes in the GnomAD database, including 4 homozygotes. There are 281 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., 56 hem., cov: 31)

Exomes 𝑓: 0.00030 ( 4 hom. 225 hem. )

Consequence

SPRY3
NM_001304990.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.948

Variant links:

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]

SPRY3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant X-155773979-A-G is Benign according to our data. Variant chrX-155773979-A-G is described in ClinVar as [Benign]. Clinvar id is 726033.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 56 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRY3	NM_001304990.2 link	c.108A>G	p.Lys36Lys	synonymous_variant	Exon 3 of 3	ENST00000695325.1	NP_001291919.1	O43610Q6ZUP3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPRY3	ENST00000695325.1 link	c.108A>G	p.Lys36Lys	synonymous_variant	Exon 3 of 3		NM_001304990.2	ENSP00000511806.1	O43610
SPRY3	ENST00000302805.7 link	c.108A>G	p.Lys36Lys	synonymous_variant	Exon 2 of 2	1		ENSP00000302978.2	O43610
SPRY3	ENST00000675360.1 link	c.108A>G	p.Lys36Lys	synonymous_variant	Exon 4 of 4			ENSP00000502489.1	O43610

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.000753

AC XY:

AN XY:

74326

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0173

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00159

AC:

399

AN:

251176

Hom.:

AF XY:

0.00156

AC XY:

212

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0212

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000304

AC:

445

AN:

1461672

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

225

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00997

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.000611

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0172

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000646

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.79

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.79

Position offset: -5

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over