chr6-146691278-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_024694.4(ADGB):c.1474G>T(p.Asp492Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000215 in 1,394,748 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: 𝑓 0.0000067 ( 0 hom., cov: 27)
Exomes 𝑓: 0.0000022 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ADGB
NM_024694.4 missense
NM_024694.4 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 6.33
Genes affected
ADGB (HGNC:21212): (androglobin) Predicted to enable calcium-dependent cysteine-type endopeptidase activity; heme binding activity; and oxygen binding activity. Predicted to be involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]
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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=0.31580812).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGB | NM_024694.4 | c.1474G>T | p.Asp492Tyr | missense_variant | 11/36 | ENST00000397944.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGB | ENST00000397944.8 | c.1474G>T | p.Asp492Tyr | missense_variant | 11/36 | 5 | NM_024694.4 | P4 | |
ADGB | ENST00000493950.6 | c.*584G>T | 3_prime_UTR_variant, NMD_transcript_variant | 9/32 | 1 | ||||
ADGB | ENST00000681847.1 | c.1474G>T | p.Asp492Tyr | missense_variant | 11/36 | A2 | |||
ADGB | ENST00000326929.8 | n.1515G>T | non_coding_transcript_exon_variant | 11/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 149282Hom.: 0 Cov.: 27 FAILED QC
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GnomAD4 exome AF: 0.00000215 AC: 3AN: 1394748Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1AN XY: 688046
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000670 AC: 1AN: 149282Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0AN XY: 72716
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?
Data not reliable, filtered out with message: AS_VQSR
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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 | Apr 25, 2023 | The c.1474G>T (p.D492Y) alteration is located in exon 11 (coding exon 11) of the ADGB gene. This alteration results from a G to T substitution at nucleotide position 1474, causing the aspartic acid (D) at amino acid position 492 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
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
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
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