7-100310432-C-A

Variant names:

• chr7-100310432-C-A
• NM_001004351.5:c.398C>A

Variant summary

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

The NM_001004351.5(SPDYE3):​c.398C>A​(p.Ser133Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDYE3 NM_001004351.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.697

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=0.1145736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPDYE3	NM_001004351.5	c.398C>A	p.Ser133Tyr	missense_variant	Exon 3 of 11	ENST00000332397.6	NP_001004351.3
SPDYE3	XM_047420404.1	c.398C>A	p.Ser133Tyr	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.398C>A	p.Ser133Tyr	missense_variant	Exon 3 of 11	1	NM_001004351.5	ENSP00000329565.6

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 612482 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 317722

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.398C>A (p.S133Y) alteration is located in exon 3 (coding exon 3) of the SPDYE3 gene. This alteration results from a C to A substitution at nucleotide position 398, causing the serine (S) at amino acid position 133 to be replaced by a tyrosine (Y). 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	0.22
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.00092	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	N
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.049
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.036	D
Vest4		0.17
MutPred		0.17		Gain of helix (P = 0.062);
MVP		0.043
MPC		2.8
ClinPred		0.23	T
Varity_R		0.078
gMVP		0.0088

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: chr7-99908055;