7-100308998-C-T

Variant names:

• chr7-100308998-C-T
• rs1164891897
• NM_001004351.5:c.131C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004351.5(SPDYE3):​c.131C>T​(p.Pro44Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 15)
• Consequence: SPDYE3 NM_001004351.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.877
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07863781).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004351.5. 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
	SPDYE3	NM_001004351.5	MANE Select	c.131C>T	p.Pro44Leu	missense	Exon 2 of 11	NP_001004351.3	A6NKU9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDYE3	ENST00000332397.6	TSL:1 MANE Select	c.131C>T	p.Pro44Leu	missense	Exon 2 of 11	ENSP00000329565.6	A6NKU9-1
	ENSG00000291178	ENST00000685541.3		n.658-8275G>A		intron	N/A
	ENSG00000291178	ENST00000685724.2		n.751-8275G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 15

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	0.19
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.0
DANN	Benign	0.86
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.00063	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.88
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.081
Sift	Benign	0.27	T
Sift4G	Uncertain	0.024	D
Vest4		0.061
MutPred		0.14		Loss of glycosylation at P44 (P = 0.0056)
MVP		0.043
MPC		2.1
ClinPred		0.065	T
GERP RS		0.19
Varity_R		0.046
gMVP		0.019
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1164891897; hg19: chr7-99906621;