X-66192205-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001367233.3(HEPH):c.1139G>A(p.Arg380Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000993 in 1,209,064 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000081 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.00010 ( 0 hom. 28 hem. )
Consequence
HEPH
NM_001367233.3 missense
NM_001367233.3 missense
Scores
8
5
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.62
Genes affected
HEPH (HGNC:4866): (hephaestin) This gene encodes a member of the multicopper oxidase protein family. The encoded protein is involved in the transport of dietary iron from epithelial cells of the intestinal lumen into the circulatory system, and may be involved in copper transport and homeostasis. In mouse, defects in this gene can lead to severe microcytic anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.83
BS2
High Hemizygotes in GnomAd4 at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HEPH | NM_001367233.3 | c.1139G>A | p.Arg380Gln | missense_variant | 7/21 | ENST00000343002.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HEPH | ENST00000343002.7 | c.1139G>A | p.Arg380Gln | missense_variant | 7/21 | 1 | NM_001367233.3 | P5 |
Frequencies
GnomAD3 genomes AF: 0.0000805 AC: 9AN: 111735Hom.: 0 Cov.: 23 AF XY: 0.0000590 AC XY: 2AN XY: 33901
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GnomAD3 exomes AF: 0.0000328 AC: 6AN: 183201Hom.: 0 AF XY: 0.0000295 AC XY: 2AN XY: 67693
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GnomAD4 exome AF: 0.000101 AC: 111AN: 1097329Hom.: 0 Cov.: 30 AF XY: 0.0000772 AC XY: 28AN XY: 362767
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GnomAD4 genome AF: 0.0000805 AC: 9AN: 111735Hom.: 0 Cov.: 23 AF XY: 0.0000590 AC XY: 2AN XY: 33901
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
1.0
.;.;.;D;D;.
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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at