Genetic Variant SPDYE3:p.Asp40Tyr (chr7-100308985-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001004351.5(SPDYE3):c.118G>T(p.Asp40Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000032 ( 0 hom., cov: 16)

Exomes 𝑓: 0.000018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPDYE3
NM_001004351.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.277

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: Uncertain_significance. The variant received 0 ACMG points.

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.118G>T	p.Asp40Tyr	missense	Exon 2 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.118G>T	p.Asp40Tyr	missense	Exon 2 of 11	ENSP00000329565.6	A6NKU9-1
ENSG00000291178	ENST00000685541.3		n.658-8262C>A		intron	N/A
ENSG00000291178	ENST00000685724.2		n.751-8262C>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000321

AC:

AN:

124482

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000616

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:

0.0000333

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000187

AC:

AN:

53552

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000497

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000177

AC:

AN:

451760

Hom.:

Cov.:

AF XY:

0.0000210

AC XY:

AN XY:

237756

show subpopulations

African (AFR)

AF:

0.0000804

AC:

AN:

12432

American (AMR)

AF:

0.00

AC:

AN:

18938

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13742

East Asian (EAS)

AF:

0.00

AC:

AN:

31160

South Asian (SAS)

AF:

0.00

AC:

AN:

45854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1972

European-Non Finnish (NFE)

AF:

0.0000257

AC:

AN:

272130

Other (OTH)

AF:

0.00

AC:

AN:

26106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000321

AC:

AN:

124482

Hom.:

Cov.:

AF XY:

0.0000171

AC XY:

AN XY:

58578

show subpopulations

African (AFR)

AF:

0.0000616

AC:

AN:

32450

American (AMR)

AF:

0.00

AC:

AN:

11134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3180

East Asian (EAS)

AF:

0.00

AC:

AN:

4224

South Asian (SAS)

AF:

0.00

AC:

AN:

3300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000333

AC:

AN:

60048

Other (OTH)

AF:

0.00

AC:

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

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

0.23

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.045

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.84

M_CAP

Benign

0.00079

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

PhyloP100

-0.28

PROVEAN

Benign

-0.75

REVEL

Benign

0.051

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Vest4

0.13

MutPred

0.19

Gain of phosphorylation at D40 (P = 0.0223)

MVP

0.043

MPC

2.7

ClinPred

0.16

GERP RS

0.19

Varity_R

0.19

gMVP

0.046

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.38

Position offset: 8

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