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GeneBe

1-197086846-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM2_SupportingBP4_Strong

The NM_018136.5(ASPM):c.10288C>T(p.Pro3430Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000395 in 152064 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

ASPM
NM_018136.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13

Links

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, gnomad allele frequency = 0.0000395 (6/152064) while in subpopulation NFE AF= 0.0000735 (5/68008). AF 95% confidence interval is 0.0000285. There are 0 homozygotes in gnomad. There are 2 alleles in male gnomad subpopulation. Median coverage is 32. This position pass quality control queck.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.04244262).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ASPMNM_018136.5 linkuse as main transcriptc.10288C>T p.Pro3430Ser missense_variant 27/28 ENST00000367409.9
ASPMNM_001206846.2 linkuse as main transcriptc.5533C>T p.Pro1845Ser missense_variant 26/27

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ASPMENST00000367409.9 linkuse as main transcriptc.10288C>T p.Pro3430Ser missense_variant 27/281 NM_018136.5 P1Q8IZT6-1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152064
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
250750
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135538
show subpopulations
Gnomad AFR exome
AF:
0.0000617
Gnomad AMR exome
AF:
0.00
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:
0.0000442
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000692
AC:
101
AN:
1459476
Hom.:
0
AF XY:
0.0000620
AC XY:
45
AN XY:
726216
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.0000847
Gnomad4 OTH exome
AF:
0.0000995
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000227
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 16, 2023The c.10288C>T (p.P3430S) alteration is located in exon 27 (coding exon 27) of the ASPM gene. This alteration results from a C to T substitution at nucleotide position 10288, causing the proline (P) at amino acid position 3430 to be replaced by a serine (S). 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
0.091
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.51
Cadd
Benign
0.86
Dann
Benign
0.18
DEOGEN2
Benign
0.013
T;.;T
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.74
T;T;T
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.042
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.065
N;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.030
N;N;N
REVEL
Benign
0.037
Sift
Benign
0.91
T;D;D
Sift4G
Benign
1.0
T;T;T
Polyphen
0.013
B;.;.
Vest4
0.089
MVP
0.29
ClinPred
0.017
T
GERP RS
2.4
Varity_R
0.017
gMVP
0.10

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: rs137887134; hg19: chr1-197055976; API