chr3-113446669-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144718.4(SPICE1):​c.2434G>A​(p.Gly812Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,612,002 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SPICE1
NM_144718.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.95
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPICE1NM_144718.4 linkc.2434G>A p.Gly812Arg missense_variant Exon 17 of 18 ENST00000295872.8 NP_653319.1 Q8N0Z3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPICE1ENST00000295872.8 linkc.2434G>A p.Gly812Arg missense_variant Exon 17 of 18 1 NM_144718.4 ENSP00000295872.4 Q8N0Z3
ENSG00000285943ENST00000649772.1 linkn.2434G>A non_coding_transcript_exon_variant Exon 17 of 39 ENSP00000497606.1
SPICE1ENST00000467618.1 linkc.433G>A p.Gly145Arg missense_variant Exon 5 of 6 5 ENSP00000420363.1 H7C5N4

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152056
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000946
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000204
AC:
51
AN:
249544
Hom.:
0
AF XY:
0.000171
AC XY:
23
AN XY:
134734
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000871
Gnomad ASJ exome
AF:
0.00150
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000661
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000275
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000142
AC:
208
AN:
1459946
Hom.:
0
Cov.:
29
AF XY:
0.000153
AC XY:
111
AN XY:
726234
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00196
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000930
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000114
Gnomad4 OTH exome
AF:
0.000249
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152056
Hom.:
0
Cov.:
32
AF XY:
0.000135
AC XY:
10
AN XY:
74256
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000946
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000337
Hom.:
1
Bravo
AF:
0.000121
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.000173
AC:
21
EpiCase
AF:
0.000327
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 11, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2434G>A (p.G812R) alteration is located in exon 17 (coding exon 16) of the SPICE1 gene. This alteration results from a G to A substitution at nucleotide position 2434, causing the glycine (G) at amino acid position 812 to be replaced by an arginine (R). 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
0.23
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.14
T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.85
D
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.42
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.8
L
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.14
Sift
Benign
0.093
T
Sift4G
Benign
0.40
T
Polyphen
0.99
D
Vest4
0.79
MutPred
0.31
Gain of MoRF binding (P = 0.0026);
MVP
0.64
MPC
0.47
ClinPred
0.20
T
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.072
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs145892348; hg19: chr3-113165516; API