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GeneBe

1-197084394-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018136.5(ASPM):c.10364A>T(p.Asn3455Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

ASPM
NM_018136.5 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Links

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=0.07763815).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ASPMNM_018136.5 linkuse as main transcriptc.10364A>T p.Asn3455Ile missense_variant 28/28 ENST00000367409.9
ASPMNM_001206846.2 linkuse as main transcriptc.5609A>T p.Asn1870Ile missense_variant 27/27

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ASPMENST00000367409.9 linkuse as main transcriptc.10364A>T p.Asn3455Ile missense_variant 28/281 NM_018136.5 P1Q8IZT6-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000320
AC:
8
AN:
250304
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135396
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000232
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000143
AC:
9
AN:
627802
Hom.:
0
AF XY:
0.0000117
AC XY:
4
AN XY:
342036
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000206
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:
0.00
Gnomad4 OTH exome
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeAug 30, 2022This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 3455 of the ASPM protein (p.Asn3455Ile). This variant is present in population databases (rs759913912, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ASPM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.26
Cadd
Benign
22
Dann
Benign
0.96
DEOGEN2
Benign
0.38
T;.;T
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.55
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.82
T;D;D
M_CAP
Uncertain
0.092
D
MetaRNN
Benign
0.078
T;T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Uncertain
2.2
M;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.23
T
PROVEAN
Pathogenic
-5.2
D;D;D
REVEL
Benign
0.13
Sift
Uncertain
0.0040
D;D;D
Sift4G
Uncertain
0.0050
D;D;D
Polyphen
0.93
P;.;.
Vest4
0.27
MutPred
0.29
Loss of disorder (P = 0.0724);.;.;
MVP
0.58
ClinPred
0.83
D
GERP RS
-1.8
Varity_R
0.26
gMVP
0.22

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.

Other links and lift over

dbSNP: rs759913912; hg19: chr1-197053524; API