Genetic Variant SPDYE3:p.Thr153Met (chr7-100310492-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001004351.5(SPDYE3):c.458C>T(p.Thr153Met) 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: 𝑓 0.0 ( 0 hom., cov: 4)

Exomes 𝑓: 0.000094 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

SPDYE3
NM_001004351.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.138

Publications

0 publications found

Variant links:

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]

SPDYE3 links:

ENSG00000291178 (HGNC:):

ENSG00000291178 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.071035266).

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.458C>T	p.Thr153Met	missense	Exon 3 of 11	NP_001004351.3	A6NKU9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPDYE3	ENST00000332397.6	TSL:1 MANE Select	c.458C>T	p.Thr153Met	missense	Exon 3 of 11	ENSP00000329565.6	A6NKU9-1
ENSG00000291178	ENST00000685541.3		n.658-9769G>A		intron	N/A
ENSG00000291178	ENST00000685724.2		n.751-9769G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

14898

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000873

AC:

AN:

34366

AF XY:

0.000113

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000161

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000935

AC:

AN:

363558

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

192392

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

10378

American (AMR)

AF:

0.00

AC:

AN:

16414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10578

East Asian (EAS)

AF:

0.0000770

AC:

AN:

25984

South Asian (SAS)

AF:

0.000518

AC:

AN:

44438

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22078

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1522

European-Non Finnish (NFE)

AF:

0.0000331

AC:

AN:

211564

Other (OTH)

AF:

0.00

AC:

AN:

20602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

14898

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

6358

African (AFR)

AF:

0.00

AC:

AN:

4096

American (AMR)

AF:

0.00

AC:

AN:

1132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

498

East Asian (EAS)

AF:

0.00

AC:

AN:

698

South Asian (SAS)

AF:

0.00

AC:

AN:

432

European-Finnish (FIN)

AF:

0.00

AC:

AN:

298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

7408

Other (OTH)

AF:

0.00

AC:

AN:

188

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.022

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.50

M_CAP

Benign

0.00067

MetaRNN

Benign

0.071

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.14

PROVEAN

Benign

-0.32

REVEL

Benign

0.036

Sift

Benign

0.41

Sift4G

Uncertain

0.0040

Vest4

0.21

MutPred

0.27

Gain of catalytic residue at T153 (P = 0.003)

MVP

0.043

MPC

1.7

ClinPred

0.011

GERP RS

0.17

Varity_R

0.034

gMVP

0.016

Mutation Taster

=300/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over