Genetic Variant SPICE1:p.Gly815Ala (chr3-113446659-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144718.4(SPICE1):c.2444G>C(p.Gly815Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SPICE1
NM_144718.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

Variant links:

Genes affected

SPICE1 (HGNC:25083): (spindle and centriole associated protein 1) Involved in metaphase plate congression; mitotic spindle assembly; and regulation of centriole replication. Located in centriole; centrosome; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

SPICE1 links:

ENSG00000285943 (HGNC:58084):

ENSG00000285943 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12192872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPICE1	NM_144718.4 link	c.2444G>C	p.Gly815Ala	missense_variant	Exon 17 of 18	ENST00000295872.8	NP_653319.1	Q8N0Z3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPICE1	ENST00000295872.8 link	c.2444G>C	p.Gly815Ala	missense_variant	Exon 17 of 18	1	NM_144718.4	ENSP00000295872.4	Q8N0Z3
ENSG00000285943	ENST00000649772.1 link	n.2444G>C		non_coding_transcript_exon_variant	Exon 17 of 39			ENSP00000497606.1
SPICE1	ENST00000467618.1 link	c.443G>C	p.Gly148Ala	missense_variant	Exon 5 of 6	5		ENSP00000420363.1	H7C5N4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460960

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726712

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2444G>C (p.G815A) alteration is located in exon 17 (coding exon 16) of the SPICE1 gene. This alteration results from a G to C substitution at nucleotide position 2444, causing the glycine (G) at amino acid position 815 to be replaced by an alanine (A). 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

Benign

0.078

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0052

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.62

M_CAP

Benign

0.0052

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.37

PROVEAN

Benign

0.46

REVEL

Benign

0.060

Sift

Benign

0.12

Sift4G

Benign

0.26

Polyphen

0.013

Vest4

0.19

MutPred

0.076

Gain of MoRF binding (P = 0.1607);

MVP

0.48

MPC

0.081

ClinPred

0.65

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.034

gMVP

0.077

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over