7-100310474-A-G

Variant names:

• chr7-100310474-A-G
• rs1192039636
• NM_001004351.5:c.440A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004351.5(SPDYE3):​c.440A>G​(p.Glu147Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 5)
• Consequence: SPDYE3 NM_001004351.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0760

Genes affected

SPDYE3 (HGNC:35462): (speedy/RINGO cell cycle regulator family member E3) Predicted to enable protein kinase binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000291178 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10491645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPDYE3	NM_001004351.5	c.440A>G	p.Glu147Gly	missense_variant	Exon 3 of 11	ENST00000332397.6	NP_001004351.3
SPDYE3	XM_047420404.1	c.440A>G	p.Glu147Gly	missense_variant	Exon 3 of 10		XP_047276360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPDYE3	ENST00000332397.6	c.440A>G	p.Glu147Gly	missense_variant	Exon 3 of 11	1	NM_001004351.5	ENSP00000329565.6

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.440A>G (p.E147G) alteration is located in exon 3 (coding exon 3) of the SPDYE3 gene. This alteration results from a A to G substitution at nucleotide position 440, causing the glutamic acid (E) at amino acid position 147 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.00049	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	N
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.041
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Vest4		0.090
MutPred		0.26		Gain of loop (P = 0.0079);
MVP		0.043
MPC		1.6
ClinPred		0.10	T
GERP RS		0.17
Varity_R		0.054
gMVP		0.010

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

LitVar

Other links and lift over

dbSNP: rs1192039636; hg19: chr7-99908097;