Genetic Variant SPDYE1:p.Pro128Ser (chr7-44002592-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001378423.2(SPDYE1):c.382C>T(p.Pro128Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,431,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. P128A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 19)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SPDYE1
NM_001378423.2 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.685

Publications

0 publications found

Variant links:

Genes affected

SPDYE1 (HGNC:16408): (speedy/RINGO cell cycle regulator family member E1) This gene is located at chromosome 7p13 which is close to the Williams Beuren syndrome chromosome region 7q11.23. [provided by RefSeq, Jul 2008]

SPDYE1 links:

POLR2J4 (HGNC:):

POLR2J4 links:

POLR2J4 (HGNC:28195): (RNA polymerase II subunit J4 (pseudogene))

POLR2J4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17369303).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378423.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPDYE1	NM_001378423.2	MANE Select	c.382C>T	p.Pro128Ser	missense splice_region	Exon 4 of 9	NP_001365352.1	A0A494C1S0
SPDYE1	NM_175064.4		c.262C>T	p.Pro88Ser	missense splice_region	Exon 2 of 7	NP_778234.2
POLR2J4	NR_003655.3		n.489+11001G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPDYE1	ENST00000693451.1	MANE Select	c.382C>T	p.Pro128Ser	missense splice_region	Exon 4 of 9	ENSP00000509569.1	A0A494C1S0
SPDYE1	ENST00000258704.3	TSL:1	c.262C>T	p.Pro88Ser	missense splice_region	Exon 2 of 7	ENSP00000258704.3	Q8NFV5
POLR2J4	ENST00000427076.5	TSL:1	n.444+11001G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1431722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33212

American (AMR)

AF:

0.00

AC:

AN:

42084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25802

East Asian (EAS)

AF:

0.00

AC:

AN:

39366

South Asian (SAS)

AF:

0.00

AC:

AN:

83564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4126

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105562

Other (OTH)

AF:

0.00

AC:

AN:

59712

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

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.047

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.71

M_CAP

Benign

0.0011

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

0.69

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.063

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.035

Polyphen

0.83

Vest4

0.087

MutPred

0.34

Gain of helix (P = 0.0022)

MVP

0.16

MPC

1.8

ClinPred

0.34

Varity_R

0.076

gMVP

0.017

Mutation Taster

=92/8

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over