Genetic Variant SPDYE4:p.Val27Met (chr17-8758304-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001394956.1(SPDYE4):c.79G>A(p.Val27Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,549,378 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000013 ( 3 hom. )

Consequence

SPDYE4
NM_001394956.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.373

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.068442434).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

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.79G>A	p.Val27Met	missense	Exon 1 of 7	NP_001381885.1	A6NLX3
	SPDYE4	NM_001128076.3		c.79G>A	p.Val27Met	missense	Exon 1 of 7	NP_001121548.1	A6NLX3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPDYE4	ENST00000689094.1	MANE Select	c.79G>A	p.Val27Met	missense	Exon 1 of 7	ENSP00000509506.1	A6NLX3
SPDYE4	ENST00000328794.10	TSL:1	c.79G>A	p.Val27Met	missense	Exon 1 of 6	ENSP00000329522.6	A6NLX3
SPDYE4	ENST00000582989.1	TSL:1	n.79G>A		non_coding_transcript_exon	Exon 1 of 6	ENSP00000464038.1	J3QR45

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152086

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000322

AC:

AN:

155402

AF XY:

0.0000489

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000896

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1397292

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

689008

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31546

American (AMR)

AF:

0.00

AC:

AN:

35396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24952

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35716

South Asian (SAS)

AF:

0.000203

AC:

AN:

78704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078038

Other (OTH)

AF:

0.00

AC:

AN:

57962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.00000658

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41394

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2082

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

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.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000355

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

0.13

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.7

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.0092

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00095

LIST_S2

Benign

0.39

M_CAP

Benign

0.0014

MetaRNN

Benign

0.068

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

PhyloP100

-0.37

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.6

REVEL

Benign

0.080

Sift

Benign

0.089

Sift4G

Benign

0.090

Polyphen

0.28

Vest4

0.11

MutPred

0.17

Loss of glycosylation at S23 (P = 0.1892)

MVP

0.040

MPC

0.24

ClinPred

0.61

GERP RS

-5.3

PromoterAI

0.012

Neutral

(source)

Varity_R

0.038

gMVP

0.066

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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