Genetic Variant SPDYE5:p.Val49Val (chr7-75494194-G-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001306141.4(SPDYE5):c.147G>T(p.Val49Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,534,956 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 28)

Exomes 𝑓: 0.0016 ( 2 hom. )

Consequence

SPDYE5
NM_001306141.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0390

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 7-75494194-G-T is Benign according to our data. Variant chr7-75494194-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2657613.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.039 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

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.147G>T	p.Val49Val	synonymous	Exon 2 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.147G>T	p.Val49Val	synonymous	Exon 2 of 9	ENSP00000485398.1	A6NIY4
	PMS2P3	ENST00000845725.1		n.435-2571C>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

246

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

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:

0.00840

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.00158

AC:

2185

AN:

1382766

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

1056

AN XY:

682320

show subpopulations

African (AFR)

AF:

0.000286

AC:

AN:

31520

American (AMR)

AF:

0.0000841

AC:

AN:

35680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25174

East Asian (EAS)

AF:

0.00

AC:

AN:

35724

South Asian (SAS)

AF:

0.00

AC:

AN:

79136

European-Finnish (FIN)

AF:

0.00799

AC:

280

AN:

35062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4062

European-Non Finnish (NFE)

AF:

0.00170

AC:

1835

AN:

1078644

Other (OTH)

AF:

0.00100

AC:

AN:

57764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

119

239

358

478

597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.00162

AC:

246

AN:

152190

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

135

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41542

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00840

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00215

AC:

146

AN:

68006

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.00216

Hom.:

Bravo

AF:

0.000960

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.25

(source)

DANN

Benign

0.54

PhyloP100

-0.039

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