Genetic Variant SPDYE3:p.Pro44Gln (chr7-100308998-C-A) – 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.131C>A(p.Pro44Gln) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P44L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000025 ( 0 hom., cov: 15)

Exomes 𝑓: 0.000028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPDYE3
NM_001004351.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.877

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=0.07184851).

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>A	p.Pro44Gln	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.131C>A	p.Pro44Gln	missense	Exon 2 of 11	ENSP00000329565.6	A6NKU9-1
ENSG00000291178	ENST00000685541.3		n.658-8275G>T		intron	N/A
ENSG00000291178	ENST00000685724.2		n.751-8275G>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000252

AC:

AN:

118890

Hom.:

Cov.:

show subpopulations

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:

0.000434

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000284

AC:

AN:

458318

Hom.:

Cov.:

AF XY:

0.0000208

AC XY:

AN XY:

240930

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12618

American (AMR)

AF:

0.00

AC:

AN:

18960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13782

East Asian (EAS)

AF:

0.00

AC:

AN:

31184

South Asian (SAS)

AF:

0.00

AC:

AN:

45972

European-Finnish (FIN)

AF:

0.000373

AC:

AN:

29452

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1990

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

278078

Other (OTH)

AF:

0.0000761

AC:

AN:

26282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.0000252

AC:

AN:

118890

Hom.:

Cov.:

AF XY:

0.0000361

AC XY:

AN XY:

55468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30830

American (AMR)

AF:

0.00

AC:

AN:

10466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3092

East Asian (EAS)

AF:

0.00

AC:

AN:

4070

South Asian (SAS)

AF:

0.00

AC:

AN:

3088

European-Finnish (FIN)

AF:

0.000434

AC:

AN:

6912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

57898

Other (OTH)

AF:

0.00

AC:

AN:

1434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.9

(source)

DANN

Benign

0.078

DEOGEN2

Benign

0.010

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.11

M_CAP

Benign

0.00042

MetaRNN

Benign

0.072

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.88

PROVEAN

Benign

-0.77

REVEL

Benign

0.081

Sift

Benign

0.31

Sift4G

Uncertain

0.042

Vest4

0.11

MutPred

0.15

Loss of glycosylation at P44 (P = 0.0056)

MVP

0.043

MPC

2.1

ClinPred

0.064

GERP RS

0.19

Varity_R

0.056

gMVP

0.025

Mutation Taster

=99/1

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