NM_032840.3:c.176A>G

Variant names:

• chr12-53075806-T-C
• rs1055499100
• NM_032840.3:c.176A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032840.3(SPRYD3):​c.176A>G​(p.His59Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPRYD3 NM_032840.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03
• Publications: 0 publications found

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

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=0.10467139).

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.176A>G	p.His59Arg	missense	Exon 3 of 11	NP_116229.1	Q8NCJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRYD3	ENST00000301463.9	TSL:1 MANE Select	c.176A>G	p.His59Arg	missense	Exon 3 of 11	ENSP00000301463.4	Q8NCJ5
	SPRYD3	ENST00000547837.5	TSL:5	c.287A>G	p.His96Arg	missense	Exon 4 of 12	ENSP00000449452.1	F8VWW7
	SPRYD3	ENST00000970163.1		c.212A>G	p.His71Arg	missense	Exon 3 of 11	ENSP00000640222.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.0093
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		5.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.061
Sift	Benign	0.36	T
Sift4G	Benign	0.082	T
Polyphen		0.010	B
Vest4		0.13
MutPred		0.45		Gain of catalytic residue at G60 (P = 0.0011)
MVP		0.15
MPC		0.95
ClinPred		0.59	D
GERP RS		4.8
Varity_R		0.16
gMVP		0.76
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs1055499100; hg19: chr12-53469590;