rs886348041

Variant names:

• chr17-8753358-C-A
• NM_001394956.1:c.617G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-8753358-C-A
• chr17-8753358-C-T

Variant summary

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

The NM_001394956.1(SPDYE4):​c.617G>T​(p.Arg206Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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. R206C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SPDYE4 NM_001394956.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367

Genes affected

SPDYE4 (HGNC:35463): (speedy/RINGO cell cycle regulator family member E4) Predicted to enable protein kinase binding activity. [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=0.12058413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPDYE4	NM_001394956.1	c.617G>T	p.Arg206Leu	missense_variant	Exon 5 of 7	ENST00000689094.1	NP_001381885.1
SPDYE4	NM_001128076.3	c.617G>T	p.Arg206Leu	missense_variant	Exon 5 of 7		NP_001121548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPDYE4	ENST00000689094.1	c.617G>T	p.Arg206Leu	missense_variant	Exon 5 of 7		NM_001394956.1	ENSP00000509506.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

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	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.025
Sift	Benign	0.048	D
Sift4G	Benign	0.22	T
Polyphen		0.43	B
Vest4		0.16
MutPred		0.36		Loss of sheet (P = 0.0457);
MVP		0.11
MPC		0.12
ClinPred		0.64	D
GERP RS		0.32
Varity_R		0.093
gMVP		0.22

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: chr17-8656676;