Variant 7-100311924-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001004351.5(SPDYE3):c.719C>T(p.Ser240Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,357,754 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 1 hom., cov: 18)

Exomes 𝑓: 0.00035 ( 86 hom. )

Failed GnomAD Quality Control

Consequence

SPDYE3
NM_001004351.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.872

Variant links:

Genes affected

SPDYE3 (HGNC:35462): (speedy/RINGO cell cycle regulator family member E3) Predicted to enable protein kinase binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SPDYE3 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.073659).

BS2

High Homozygotes in GnomAdExome4 at 86 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPDYE3	NM_001004351.5 linkuse as main transcript	c.719C>T	p.Ser240Leu	missense_variant	4/11	ENST00000332397.6
SPDYE3	XM_047420404.1 linkuse as main transcript	c.719C>T	p.Ser240Leu	missense_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPDYE3	ENST00000332397.6 linkuse as main transcript	c.719C>T	p.Ser240Leu	missense_variant	4/11	1	NM_001004351.5	P1	A6NKU9-1
	ENST00000685724.2 linkuse as main transcript	n.751-11201G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000288

AC:

AN:

124872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000766

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000205

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000584

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000432

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000187

AC:

AN:

117616

Hom.:

AF XY:

0.000173

AC XY:

AN XY:

63602

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000941

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000551

Gnomad FIN exome

AF:

0.000459

Gnomad NFE exome

AF:

0.000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000348

AC:

473

AN:

1357754

Hom.:

Cov.:

AF XY:

0.000339

AC XY:

229

AN XY:

674536

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000475

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000859

Gnomad4 FIN exome

AF:

0.000336

Gnomad4 NFE exome

AF:

0.000417

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000288

AC:

AN:

124872

Hom.:

Cov.:

AF XY:

0.000299

AC XY:

AN XY:

60250

show subpopulations

Gnomad4 AFR

AF:

0.000105

Gnomad4 AMR

AF:

0.0000766

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000205

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000584

Gnomad4 NFE

AF:

0.000432

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000320

Hom.:

ExAC

AF:

0.000136

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.719C>T (p.S240L) alteration is located in exon 4 (coding exon 4) of the SPDYE3 gene. This alteration results from a C to T substitution at nucleotide position 719, causing the serine (S) at amino acid position 240 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.030

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.0035

LIST_S2

Benign

0.82

M_CAP

Benign

0.0013

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.89

REVEL

Benign

0.037

Sift

Pathogenic

0.0

Sift4G

Benign

0.14

Vest4

0.15

MVP

0.043

MPC

1.3

ClinPred

0.094

Varity_R

0.13

gMVP

0.032

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over