chr9-116487408-T-A

Variant summary

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

The NM_001365068.1(ASTN2):​c.3448A>T​(p.Ser1150Cys) 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 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1150G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ASTN2
NM_001365068.1 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.57
Variant links:
Genes affected
ASTN2 (HGNC:17021): (astrotactin 2) This gene encodes a protein that is expressed in the brain and may function in neuronal migration, based on functional studies of the related astrotactin 1 gene in human and mouse. A deletion at this locus has been associated with schizophrenia. Multiple transcript variants encoding different proteins have been found for this locus. [provided by RefSeq, May 2010]

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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=0.26083678).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ASTN2NM_001365068.1 linkuse as main transcriptc.3448A>T p.Ser1150Cys missense_variant 20/23 ENST00000313400.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ASTN2ENST00000313400.9 linkuse as main transcriptc.3448A>T p.Ser1150Cys missense_variant 20/235 NM_001365068.1 A2O75129-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461818
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727218
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsSep 22, 2023The c.3295A>T (p.S1099C) alteration is located in exon 19 (coding exon 19) of the ASTN2 gene. This alteration results from a A to T substitution at nucleotide position 3295, causing the serine (S) at amino acid position 1099 to be replaced by a cysteine (C). 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
0.26
BayesDel_addAF
Benign
0.00049
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.044
T;.;.;.;.;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.88
D;D;D;D;D;D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.26
T;T;T;T;T;T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
0.81
L;.;.;.;.;.
MutationTaster
Benign
0.99
D;D;D;D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.4
N;N;N;N;N;N
REVEL
Benign
0.14
Sift
Uncertain
0.028
D;D;D;D;D;D
Sift4G
Uncertain
0.043
D;D;D;D;D;D
Polyphen
0.68
P;D;D;.;D;D
Vest4
0.54
MutPred
0.33
Loss of disorder (P = 0.0043);.;.;.;.;.;
MVP
0.043
MPC
0.23
ClinPred
0.67
D
GERP RS
5.5
Varity_R
0.39
gMVP
0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-119249687; API