NM_001002036.4:c.829A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001002036.4(ASTL):​c.829A>C​(p.Lys277Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,594,978 control chromosomes in the GnomAD database, including 114,785 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 10521 hom., cov: 32)
Exomes 𝑓: 0.37 ( 104264 hom. )

Consequence

ASTL
NM_001002036.4 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.866

Publications

33 publications found
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=1.5303493E-4).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASTLNM_001002036.4 linkc.829A>C p.Lys277Gln missense_variant Exon 8 of 9 ENST00000342380.3 NP_001002036.3 Q6HA08
ASTLXM_011511205.3 linkc.844A>C p.Lys282Gln missense_variant Exon 7 of 8 XP_011509507.1
ASTLXM_011511207.3 linkc.790A>C p.Lys264Gln missense_variant Exon 7 of 8 XP_011509509.1
ASTLXM_011511208.3 linkc.734+195A>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.829A>C p.Lys277Gln missense_variant Exon 8 of 9 1 NM_001002036.4 ENSP00000343674.2 Q6HA08

Frequencies

GnomAD3 genomes
AF:
0.361
AC:
54879
AN:
151938
Hom.:
10506
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.296
Gnomad AMI
AF:
0.490
Gnomad AMR
AF:
0.401
Gnomad ASJ
AF:
0.237
Gnomad EAS
AF:
0.612
Gnomad SAS
AF:
0.270
Gnomad FIN
AF:
0.492
Gnomad MID
AF:
0.158
Gnomad NFE
AF:
0.365
Gnomad OTH
AF:
0.320
GnomAD2 exomes
AF:
0.393
AC:
96751
AN:
246106
AF XY:
0.380
show subpopulations
Gnomad AFR exome
AF:
0.292
Gnomad AMR exome
AF:
0.509
Gnomad ASJ exome
AF:
0.240
Gnomad EAS exome
AF:
0.628
Gnomad FIN exome
AF:
0.489
Gnomad NFE exome
AF:
0.367
Gnomad OTH exome
AF:
0.354
GnomAD4 exome
AF:
0.374
AC:
539292
AN:
1442922
Hom.:
104264
Cov.:
37
AF XY:
0.368
AC XY:
263155
AN XY:
714572
show subpopulations
African (AFR)
AF:
0.285
AC:
9425
AN:
33042
American (AMR)
AF:
0.499
AC:
21833
AN:
43752
Ashkenazi Jewish (ASJ)
AF:
0.240
AC:
6152
AN:
25600
East Asian (EAS)
AF:
0.575
AC:
22579
AN:
39274
South Asian (SAS)
AF:
0.264
AC:
22381
AN:
84886
European-Finnish (FIN)
AF:
0.488
AC:
25943
AN:
53130
Middle Eastern (MID)
AF:
0.185
AC:
865
AN:
4680
European-Non Finnish (NFE)
AF:
0.372
AC:
409262
AN:
1099224
Other (OTH)
AF:
0.351
AC:
20852
AN:
59334
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.468
Heterozygous variant carriers
0
16232
32465
48697
64930
81162
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
13192
26384
39576
52768
65960
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.361
AC:
54944
AN:
152056
Hom.:
10521
Cov.:
32
AF XY:
0.366
AC XY:
27207
AN XY:
74316
show subpopulations
African (AFR)
AF:
0.297
AC:
12301
AN:
41456
American (AMR)
AF:
0.402
AC:
6147
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.237
AC:
824
AN:
3470
East Asian (EAS)
AF:
0.612
AC:
3157
AN:
5162
South Asian (SAS)
AF:
0.270
AC:
1301
AN:
4820
European-Finnish (FIN)
AF:
0.492
AC:
5206
AN:
10584
Middle Eastern (MID)
AF:
0.167
AC:
49
AN:
294
European-Non Finnish (NFE)
AF:
0.365
AC:
24839
AN:
67960
Other (OTH)
AF:
0.319
AC:
673
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1786
3572
5357
7143
8929
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
534
1068
1602
2136
2670
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.361
Hom.:
33972
Bravo
AF:
0.360
TwinsUK
AF:
0.365
AC:
1355
ALSPAC
AF:
0.371
AC:
1431
ESP6500AA
AF:
0.294
AC:
1297
ESP6500EA
AF:
0.362
AC:
3115
ExAC
AF:
0.383
AC:
46466
Asia WGS
AF:
0.383
AC:
1331
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
15
DANN
Benign
0.94
DEOGEN2
Benign
0.10
T
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.40
T
MetaRNN
Benign
0.00015
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.52
N
PhyloP100
0.87
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.11
Sift
Benign
0.079
T
Sift4G
Benign
0.32
T
Polyphen
0.026
B
Vest4
0.049
MPC
0.18
ClinPred
0.0070
T
GERP RS
-2.3
Varity_R
0.26
gMVP
0.57
Mutation Taster
=96/4
polymorphism (auto)

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

Other links and lift over

dbSNP: rs1657502; hg19: chr2-96795608; COSMIC: COSV60904250; COSMIC: COSV60904250; API