7-100308998-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

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

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=0.07863781).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPDYE3	NM_001004351.5	c.131C>T	p.Pro44Leu	missense_variant	Exon 2 of 11	ENST00000332397.6	NP_001004351.3
SPDYE3	XM_047420404.1	c.131C>T	p.Pro44Leu	missense_variant	Exon 2 of 10		XP_047276360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPDYE3	ENST00000332397.6	c.131C>T	p.Pro44Leu	missense_variant	Exon 2 of 11	1	NM_001004351.5	ENSP00000329565.6

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 15

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.131C>T (p.P44L) alteration is located in exon 2 (coding exon 2) of the SPDYE3 gene. This alteration results from a C to T substitution at nucleotide position 131, causing the proline (P) at amino acid position 44 to be replaced by a leucine (L). 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	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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-99906621;