dbSNP rs778846052: SPRYD3:p.Gly221Val (chr12-53073317-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032840.3(SPRYD3):c.662G>T(p.Gly221Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000055 in 1,455,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G221D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000053 ( 0 hom. )

Consequence

SPRYD3
NM_032840.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64

Publications

0 publications found

Variant links:

Genes affected

SPRYD3 (HGNC:25920): (SPRY domain containing 3) Predicted to be involved in cell surface receptor signaling pathway and cytoskeleton organization. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPRYD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2234096).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032840.3. 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
	SPRYD3	NM_032840.3	MANE Select	c.662G>T	p.Gly221Val	missense	Exon 6 of 11	NP_116229.1	Q8NCJ5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPRYD3	ENST00000301463.9	TSL:1 MANE Select	c.662G>T	p.Gly221Val	missense	Exon 6 of 11	ENSP00000301463.4	Q8NCJ5
SPRYD3	ENST00000547837.5	TSL:5	c.773G>T	p.Gly258Val	missense	Exon 7 of 12	ENSP00000449452.1	F8VWW7
SPRYD3	ENST00000970163.1		c.698G>T	p.Gly233Val	missense	Exon 6 of 11	ENSP00000640222.1

Frequencies

GnomAD3 genomes

AF:

0.00000694

AC:

AN:

144098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000711

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000888

AC:

AN:

225180

AF XY:

0.00000827

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000620

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000534

AC:

AN:

1311286

Hom.:

Cov.:

AF XY:

0.00000463

AC XY:

AN XY:

648620

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29462

American (AMR)

AF:

0.000181

AC:

AN:

38678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20382

East Asian (EAS)

AF:

0.00

AC:

AN:

27964

South Asian (SAS)

AF:

0.00

AC:

AN:

81808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5026

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1014882

Other (OTH)

AF:

0.00

AC:

AN:

50762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000694

AC:

AN:

144098

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69826

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39552

American (AMR)

AF:

0.0000711

AC:

AN:

14060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3398

East Asian (EAS)

AF:

0.00

AC:

AN:

4334

South Asian (SAS)

AF:

0.00

AC:

AN:

4124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

298

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66176

Other (OTH)

AF:

0.00

AC:

AN:

2012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

Eigen

Benign

-0.063

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0037

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

3.6

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.060

REVEL

Uncertain

0.30

Sift

Benign

0.21

Sift4G

Benign

0.27

Polyphen

0.041

Vest4

0.61

MutPred

0.46

Gain of catalytic residue at R222 (P = 0.021)

MVP

0.12

MPC

1.2

ClinPred

0.41

GERP RS

5.2

Varity_R

0.28

gMVP

0.89

Mutation Taster

=65/35

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over