chr1-166989750-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032858.3(MAEL):ā€‹c.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

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.94
Variant links:
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]

Genome browser will be placed here

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
MAELNM_032858.3 linkuse as main transcriptc.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
MAELENST00000367872.9 linkuse as main transcriptc.146A>G p.Glu49Gly missense_variant 2/121 NM_032858.3 ENSP00000356846 P1Q96JY0-1
MAELENST00000622874.4 linkuse as main transcriptc.-23A>G 5_prime_UTR_variant 3/131 ENSP00000482771
MAELENST00000367870.6 linkuse as main transcriptc.132+266A>G intron_variant 1 ENSP00000356844 Q96JY0-2
MAELENST00000447624.1 linkuse as main transcriptc.132+266A>G intron_variant 3 ENSP00000402143

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152068
Hom.:
0
Cov.:
31
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
GnomAD4 exome
AF:
0.0000109
AC:
16
AN:
1461640
Hom.:
0
Cov.:
31
AF XY:
0.0000151
AC XY:
11
AN XY:
727072
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:
0.0000144
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152068
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74266
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
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsApr 19, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.092
T
BayesDel_noAF
Benign
-0.37
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T
Eigen
Uncertain
0.27
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.97
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-4.4
D
REVEL
Benign
0.17
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.019
D
Polyphen
0.65
P
Vest4
0.34
MVP
0.57
MPC
0.61
ClinPred
0.98
D
GERP RS
5.4
Varity_R
0.56
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.31
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.31
Position offset: -13

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: rs144606344; hg19: chr1-166958987; API