chr16-4657290-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015246.4(MGRN1):c.488A>G(p.Tyr163Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,614,144 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
MGRN1
NM_015246.4 missense
NM_015246.4 missense
Scores
2
6
7
Clinical Significance
Conservation
PhyloP100: 4.24
Genes affected
MGRN1 (HGNC:20254): (mahogunin ring finger 1) Enables ubiquitin-protein transferase activity. Involved in endosome to lysosome transport; negative regulation of signal transduction; and protein monoubiquitination. Located in several cellular components, including early endosome; endoplasmic reticulum; 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 | UniProt |
---|---|---|---|---|---|---|---|
MGRN1 | NM_015246.4 | c.488A>G | p.Tyr163Cys | missense_variant | 5/17 | ENST00000262370.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MGRN1 | ENST00000262370.12 | c.488A>G | p.Tyr163Cys | missense_variant | 5/17 | 1 | NM_015246.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249558Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135398
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461814Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727216
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74504
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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 | Oct 26, 2022 | The c.488A>G (p.Y163C) alteration is located in exon 5 (coding exon 5) of the MGRN1 gene. This alteration results from a A to G substitution at nucleotide position 488, causing the tyrosine (Y) at amino acid position 163 to be replaced by a cysteine (C). 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;.;.;.;D;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D;D;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D;D;D;D;D;D;D;D
Polyphen
1.0, 1.0, 1.0
.;D;D;.;D;D;D;.
Vest4
0.64, 0.61, 0.60, 0.61, 0.61
MutPred
0.48
.;Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);.;
MVP
MPC
0.053
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at