Genetic Variant NM_032840.3:c.662G>A (chr12-53073317-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032840.3(SPRYD3):c.662G>A(p.Gly221Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000763 in 1,311,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. G221V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 7.6e-7 ( 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23612806).

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>A	p.Gly221Asp	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>A	p.Gly221Asp	missense	Exon 6 of 11	ENSP00000301463.4	Q8NCJ5
SPRYD3	ENST00000547837.5	TSL:5	c.773G>A	p.Gly258Asp	missense	Exon 7 of 12	ENSP00000449452.1	F8VWW7
SPRYD3	ENST00000970163.1		c.698G>A	p.Gly233Asp	missense	Exon 6 of 11	ENSP00000640222.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000444

AC:

AN:

225180

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000993

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.63e-7

AC:

AN:

1311286

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

648620

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29462

American (AMR)

AF:

0.00

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:

9.85e-7

AC:

AN:

1014882

Other (OTH)

AF:

0.00

AC:

AN:

50762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

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

Pathogenic

0.66

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Benign

-0.057

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.0028

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

3.6

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.99

REVEL

Benign

0.091

Sift

Benign

0.13

Sift4G

Benign

0.29

Polyphen

0.23

Vest4

0.65

MutPred

0.39

Gain of catalytic residue at D225 (P = 0.0377)

MVP

0.068

MPC

1.4

ClinPred

0.33

GERP RS

5.2

Varity_R

0.27

gMVP

0.93

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over