chr1-166989750-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032858.3(MAEL):āc.146A>Gā(p.Glu49Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,708 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 (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 31)
Exomes š: 0.000011 ( 0 hom. )
Consequence
MAEL
NM_032858.3 missense
NM_032858.3 missense
Scores
2
6
11
Clinical Significance
Conservation
PhyloP100: 5.94
Genes affected
MAEL (HGNC:25929): (maelstrom spermatogenic transposon silencer) Predicted to enable sequence-specific DNA binding activity. Predicted to be involved in gamete generation; negative regulation of macromolecule metabolic process; and piRNA metabolic process. Predicted to act upstream of or within several processes, including homologous chromosome pairing at meiosis; intrinsic apoptotic signaling pathway in response to DNA damage; and negative regulation of macromolecule metabolic process. Predicted to be located in piP-body. Predicted to be active in P granule and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAEL | NM_032858.3 | c.146A>G | p.Glu49Gly | missense_variant | 2/12 | ENST00000367872.9 | NP_116247.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAEL | ENST00000367872.9 | c.146A>G | p.Glu49Gly | missense_variant | 2/12 | 1 | NM_032858.3 | ENSP00000356846 | P1 | |
MAEL | ENST00000622874.4 | c.-23A>G | 5_prime_UTR_variant | 3/13 | 1 | ENSP00000482771 | ||||
MAEL | ENST00000367870.6 | c.132+266A>G | intron_variant | 1 | ENSP00000356844 | |||||
MAEL | ENST00000447624.1 | c.132+266A>G | intron_variant | 3 | ENSP00000402143 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152068Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461640Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727072
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152068Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74266
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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 submitter | clinical testing | Ambry Genetics | Apr 19, 2023 | The c.146A>G (p.E49G) alteration is located in exon 2 (coding exon 2) of the MAEL gene. This alteration results from a A to G substitution at nucleotide position 146, causing the glutamic acid (E) at amino acid position 49 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -13
Find out detailed SpliceAI scores and Pangolin per-transcript scores at