rs28939076
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_014585.6(SLC40A1):c.230C>A(p.Ala77Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
SLC40A1
NM_014585.6 missense
NM_014585.6 missense
Scores
11
7
1
Clinical Significance
Conservation
PhyloP100: 8.07
Genes affected
SLC40A1 (HGNC:10909): (solute carrier family 40 member 1) The protein encoded by this gene is a cell membrane protein that may be involved in iron export from duodenal epithelial cells. Defects in this gene are a cause of hemochromatosis type 4 (HFE4). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PM1
?
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_014585.6
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.945
PP5
?
Variant 2-189575202-G-T is Pathogenic according to our data. Variant chr2-189575202-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 5411.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC40A1 | NM_014585.6 | c.230C>A | p.Ala77Asp | missense_variant | 3/8 | ENST00000261024.7 | |
SLC40A1 | XM_047444066.1 | c.110C>A | p.Ala37Asp | missense_variant | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC40A1 | ENST00000261024.7 | c.230C>A | p.Ala77Asp | missense_variant | 3/8 | 1 | NM_014585.6 | P1 | |
SLC40A1 | ENST00000479598.5 | n.511C>A | non_coding_transcript_exon_variant | 3/4 | 1 | ||||
SLC40A1 | ENST00000427241.5 | c.230C>A | p.Ala77Asp | missense_variant | 5/8 | 5 | |||
SLC40A1 | ENST00000418714.1 | n.671C>A | non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hemochromatosis type 4 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2006 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
A
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;.
Polyphen
D;.
Vest4
MutPred
Loss of sheet (P = 0.0483);Loss of sheet (P = 0.0483);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at