chr6-37646268-C-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_153487.4(MDGA1):āc.2154G>Cā(p.Glu718Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,606,184 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.0080 ( 18 hom., cov: 32)
Exomes š: 0.0012 ( 20 hom. )
Consequence
MDGA1
NM_153487.4 missense
NM_153487.4 missense
Scores
1
9
8
Clinical Significance
Conservation
PhyloP100: 2.62
Genes affected
MDGA1 (HGNC:19267): (MAM domain containing glycosylphosphatidylinositol anchor 1) This gene encodes a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that is expressed predominantly in the developing nervous system. In addition to possessing several cell adhesion molecule-like domains, the mature protein has six Ig-like domains, a single fibronectin type III domain, a MAM domain and a C-terminal GPI-anchoring site. Studies in other mammals suggest this protein plays a role in cell adhesion, migration, and axon guidance and, in the developing brain, neuronal migration. In humans, this gene is associated with bipolar disorder and schizophrenia. [provided by RefSeq, Oct 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0096515715).
BP6
Variant 6-37646268-C-G is Benign according to our data. Variant chr6-37646268-C-G is described in ClinVar as [Benign]. Clinvar id is 786087.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00798 (1216/152316) while in subpopulation AFR AF= 0.0265 (1102/41562). AF 95% confidence interval is 0.0252. There are 18 homozygotes in gnomad4. There are 612 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 18 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MDGA1 | NM_153487.4 | c.2154G>C | p.Glu718Asp | missense_variant | 11/17 | ENST00000434837.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MDGA1 | ENST00000434837.8 | c.2154G>C | p.Glu718Asp | missense_variant | 11/17 | 1 | NM_153487.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00797 AC: 1213AN: 152198Hom.: 18 Cov.: 32
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GnomAD3 exomes AF: 0.00276 AC: 659AN: 238402Hom.: 3 AF XY: 0.00261 AC XY: 337AN XY: 129036
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GnomAD4 exome AF: 0.00119 AC: 1731AN: 1453868Hom.: 20 Cov.: 31 AF XY: 0.00125 AC XY: 901AN XY: 722104
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GnomAD4 genome AF: 0.00798 AC: 1216AN: 152316Hom.: 18 Cov.: 32 AF XY: 0.00822 AC XY: 612AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 25, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
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
Uncertain
D;D;D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Uncertain
D;.;D
Polyphen
D;.;.
Vest4
MutPred
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
MPC
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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