Genetic Variant SPDYE4:p.Tyr199Cys (chr17-8753379-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394956.1(SPDYE4):c.596A>G(p.Tyr199Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,564,120 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

SPDYE4
NM_001394956.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.183

Publications

0 publications found

Variant links:

Genes affected

SPDYE4 (HGNC:35463): (speedy/RINGO cell cycle regulator family member E4) Predicted to enable protein kinase binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SPDYE4 links:

ENSG00000297596 (HGNC:):

ENSG00000297596 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.060202956).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394956.1. 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
	SPDYE4	NM_001394956.1	MANE Select	c.596A>G	p.Tyr199Cys	missense	Exon 5 of 7	NP_001381885.1	A6NLX3
	SPDYE4	NM_001128076.3		c.596A>G	p.Tyr199Cys	missense	Exon 5 of 7	NP_001121548.1	A6NLX3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPDYE4	ENST00000689094.1	MANE Select	c.596A>G	p.Tyr199Cys	missense	Exon 5 of 7	ENSP00000509506.1	A6NLX3
SPDYE4	ENST00000328794.10	TSL:1	c.596A>G	p.Tyr199Cys	missense	Exon 5 of 6	ENSP00000329522.6	A6NLX3
SPDYE4	ENST00000582989.1	TSL:1	n.*475A>G		non_coding_transcript_exon	Exon 5 of 6	ENSP00000464038.1	J3QR45

Frequencies

GnomAD3 genomes

AF:

0.000203

AC:

AN:

147916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000912

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000253

Gnomad OTH

AF:

0.000488

GnomAD2 exomes

AF:

0.000251

AC:

AN:

210838

AF XY:

0.000256

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:

0.00113

Gnomad NFE exome

AF:

0.000324

Gnomad OTH exome

AF:

0.000185

GnomAD4 exome

AF:

0.000134

AC:

190

AN:

1416082

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

701582

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32814

American (AMR)

AF:

0.00

AC:

AN:

38868

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24738

East Asian (EAS)

AF:

0.00

AC:

AN:

36962

South Asian (SAS)

AF:

0.00

AC:

AN:

83190

European-Finnish (FIN)

AF:

0.00124

AC:

AN:

49994

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.000108

AC:

117

AN:

1085722

Other (OTH)

AF:

0.000172

AC:

AN:

58180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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

AF:

0.000203

AC:

AN:

148038

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

AN XY:

72040

show subpopulations

African (AFR)

AF:

0.0000246

AC:

AN:

40650

American (AMR)

AF:

0.000137

AC:

AN:

14550

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3434

East Asian (EAS)

AF:

0.00

AC:

AN:

4712

South Asian (SAS)

AF:

0.00

AC:

AN:

4472

European-Finnish (FIN)

AF:

0.000912

AC:

AN:

9868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000253

AC:

AN:

67096

Other (OTH)

AF:

0.000483

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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:

0.000213

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.000249

AC:

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

0.30

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.081

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.52

M_CAP

Benign

0.0021

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

-0.18

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.035

Sift

Benign

0.14

Sift4G

Benign

0.17

Polyphen

0.97

Vest4

0.23

MVP

0.18

MPC

0.35

ClinPred

0.16

GERP RS

0.11

Varity_R

0.14

gMVP

0.14

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over