chr1-166992745-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032858.3(MAEL):​c.385C>T​(p.His129Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,996 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MAEL
NM_032858.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.84
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33845448).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAELNM_032858.3 linkc.385C>T p.His129Tyr missense_variant Exon 4 of 12 ENST00000367872.9 NP_116247.1 Q96JY0-1A0A140VJP0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAELENST00000367872.9 linkc.385C>T p.His129Tyr missense_variant Exon 4 of 12 1 NM_032858.3 ENSP00000356846.4 Q96JY0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1458996
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725758
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.385C>T (p.H129Y) alteration is located in exon 4 (coding exon 4) of the MAEL gene. This alteration results from a C to T substitution at nucleotide position 385, causing the histidine (H) at amino acid position 129 to be replaced by a tyrosine (Y). 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
0.097
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.080
.;.;T;T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.81
T;T;T;T
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.34
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.81
.;.;L;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.99
.;N;N;N
REVEL
Benign
0.18
Sift
Benign
0.042
.;D;D;D
Sift4G
Benign
0.18
T;T;T;T
Polyphen
0.99
.;.;D;.
Vest4
0.59
MutPred
0.51
.;.;Gain of stability (P = 0.0053);.;
MVP
0.65
MPC
0.67
ClinPred
0.86
D
GERP RS
5.5
Varity_R
0.19
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs375663463; hg19: chr1-166961982; API