rs374096283

Variant names:

• chr12-53073365-C-A
• NM_032840.3:c.614G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-53073365-C-A
• chr12-53073365-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032840.3(SPRYD3):​c.614G>T​(p.Arg205Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,442,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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. R205H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPRYD3 NM_032840.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07421312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRYD3	NM_032840.3	c.614G>T	p.Arg205Leu	missense_variant	Exon 6 of 11	ENST00000301463.9	NP_116229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRYD3	ENST00000301463.9	c.614G>T	p.Arg205Leu	missense_variant	Exon 6 of 11	1	NM_032840.3	ENSP00000301463.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1442564 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 715406

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: 0.0000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0026	T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.33	N;N
REVEL	Benign	0.13
Sift	Benign	0.53	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.0030	B;.
Vest4		0.15
MutPred		0.48		Gain of catalytic residue at R205 (P = 0.0112);.;
MVP		0.043
MPC		0.97
ClinPred		0.37	T
GERP RS		5.0
Varity_R		0.20
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-53467149;