12-53066438-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032840.3(SPRYD3):​c.1070G>A​(p.Arg357Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R357P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SPRYD3
NM_032840.3 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.48
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPRYD3NM_032840.3 linkc.1070G>A p.Arg357Gln missense_variant Exon 10 of 11 ENST00000301463.9 NP_116229.1 Q8NCJ5A0A024RAX4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPRYD3ENST00000301463.9 linkc.1070G>A p.Arg357Gln missense_variant Exon 10 of 11 1 NM_032840.3 ENSP00000301463.4 Q8NCJ5
SPRYD3ENST00000547837.5 linkc.1181G>A p.Arg394Gln missense_variant Exon 11 of 12 5 ENSP00000449452.1 F8VWW7
SPRYD3ENST00000547257.1 linkn.-80G>A upstream_gene_variant 5 ENSP00000448845.1 H0YI85
SPRYD3ENST00000537540.1 linkn.*522G>A downstream_gene_variant 2 ENSP00000446156.1 B7Z1Y3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249472
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135012
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000895
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461880
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.058
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0026
T;T
Eigen
Benign
-0.11
Eigen_PC
Benign
0.064
FATHMM_MKL
Benign
0.72
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-0.69
N;.
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.080
N;N
REVEL
Benign
0.078
Sift
Benign
0.49
T;T
Sift4G
Benign
0.59
T;T
Polyphen
0.30
B;.
Vest4
0.43
MutPred
0.47
Gain of catalytic residue at V362 (P = 0.021);.;
MVP
0.10
MPC
0.91
ClinPred
0.29
T
GERP RS
4.9
Varity_R
0.061
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.98
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.98
Position offset: -2

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.

Other links and lift over

dbSNP: rs372927015; hg19: chr12-53460222; API