Genetic Variant SPDYE5:p.Pro82Gln (chr7-75495240-C-A) – 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_001306141.4(SPDYE5):c.245C>A(p.Pro82Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000599 in 1,596,798 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00063 ( 1 hom. )

Consequence

SPDYE5
NM_001306141.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.188

Publications

1 publications found

Variant links:

Genes affected

SPDYE5 (HGNC:35464): (speedy/RINGO cell cycle regulator family member E5) Predicted to enable protein kinase binding activity. Predicted to be involved in positive regulation of cyclin-dependent protein serine/threonine kinase activity. [provided by Alliance of Genome Resources, Apr 2022]

SPDYE5 links:

PMS2P3 (HGNC:):

PMS2P3 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=0.026126772).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001306141.4. 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
	SPDYE5	NM_001306141.4	MANE Select	c.245C>A	p.Pro82Gln	missense	Exon 3 of 9	NP_001293070.1	A6NIY4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDYE5	ENST00000625065.4	TSL:5 MANE Select	c.245C>A	p.Pro82Gln	missense	Exon 3 of 9	ENSP00000485398.1	A6NIY4
	PMS2P3	ENST00000845725.1		n.435-3617G>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000336

AC:

AN:

151694

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000969

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:

0.000692

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000324

AC:

AN:

218876

AF XY:

0.000343

show subpopulations

Gnomad AFR exome

AF:

0.000158

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000917

Gnomad NFE exome

AF:

0.000646

Gnomad OTH exome

AF:

0.000352

GnomAD4 exome

AF:

0.000627

AC:

906

AN:

1444986

Hom.:

Cov.:

AF XY:

0.000598

AC XY:

430

AN XY:

719202

show subpopulations

African (AFR)

AF:

0.0000898

AC:

AN:

33408

American (AMR)

AF:

0.00

AC:

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86146

European-Finnish (FIN)

AF:

0.0000256

AC:

AN:

39128

Middle Eastern (MID)

AF:

0.000241

AC:

AN:

4142

European-Non Finnish (NFE)

AF:

0.000800

AC:

889

AN:

1111668

Other (OTH)

AF:

0.000183

AC:

AN:

60118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

120

180

240

300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

114

152

190

<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:

0.000336

AC:

AN:

151812

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.0000966

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000692

AC:

AN:

67920

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.000256

Hom.:

Bravo

AF:

0.000314

ExAC

AF:

0.000203

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

-0.29

BayesDel_noAF

Benign

-0.29

CADD

Benign

7.6

(source)

DANN

Benign

0.62

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.58

MetaRNN

Benign

0.026

PhyloP100

0.19

PrimateAI

Uncertain

0.49

Sift4G

Uncertain

0.0040

Vest4

0.18

MVP

0.030

GERP RS

-1.1

Varity_R

0.092

gMVP

0.031

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over