rs144062488

Variant summary

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

The NM_001002036.4(ASTL):​c.838G>C​(p.Gly280Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G280S) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)

Consequence

ASTL
NM_001002036.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.158
Variant links:
Genes affected
ASTL (HGNC:31704): (astacin like metalloendopeptidase) Predicted to enable aspartic-type peptidase activity; glutamic-type peptidase activity; and metalloendopeptidase activity. Predicted to be involved in several processes, including negative regulation of binding activity of sperm to zona pellucida; positive regulation of protein processing; and prevention of polyspermy. Predicted to be located in cortical granule and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.2446205).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASTLNM_001002036.4 linkc.838G>C p.Gly280Arg missense_variant Exon 8 of 9 ENST00000342380.3 NP_001002036.3 Q6HA08
ASTLXM_011511205.3 linkc.853G>C p.Gly285Arg missense_variant Exon 7 of 8 XP_011509507.1
ASTLXM_011511207.3 linkc.799G>C p.Gly267Arg missense_variant Exon 7 of 8 XP_011509509.1
ASTLXM_011511208.3 linkc.734+204G>C intron_variant Intron 6 of 6 XP_011509510.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASTLENST00000342380.3 linkc.838G>C p.Gly280Arg missense_variant Exon 8 of 9 1 NM_001002036.4 ENSP00000343674.2 Q6HA08

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152202
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000411
AC:
1
AN:
243214
Hom.:
0
AF XY:
0.00000762
AC XY:
1
AN XY:
131218
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.00000907
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152202
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
14
DANN
Uncertain
0.98
DEOGEN2
Benign
0.045
T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.64
T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.58
N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.052
Sift
Benign
0.11
T
Sift4G
Benign
0.31
T
Polyphen
0.64
P
Vest4
0.12
MutPred
0.49
Gain of MoRF binding (P = 0.0073);
MVP
0.59
MPC
0.30
ClinPred
0.14
T
GERP RS
2.3
Varity_R
0.042
gMVP
0.46

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: rs144062488; hg19: chr2-96795599; API