rs35790721
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000519.4(HBD):c.365A>T(p.Glu122Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as other (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: not found (cov: 32)
Consequence
HBD
NM_000519.4 missense
NM_000519.4 missense
Scores
3
3
8
Clinical Significance
Conservation
PhyloP100: 1.65
Genes affected
HBD (HGNC:4829): (hemoglobin subunit delta) The delta (HBD) and beta (HBB) genes are normally expressed in the adult: two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin. Two alpha chains plus two delta chains constitute HbA-2, which with HbF comprises the remaining 3% of adult hemoglobin. Five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5'-epsilon--Ggamma--Agamma--delta--beta-3'. Mutations in the delta-globin gene are associated with beta-thalassemia. [provided by RefSeq, Jul 2008]
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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 |
---|---|---|---|---|---|---|---|
HBD | NM_000519.4 | c.365A>T | p.Glu122Val | missense_variant | 3/3 | ENST00000650601.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBD | ENST00000650601.1 | c.365A>T | p.Glu122Val | missense_variant | 3/3 | NM_000519.4 | P1 | ||
HBD | ENST00000643122.1 | c.365A>T | p.Glu122Val | missense_variant | 4/4 | P1 | |||
HBD | ENST00000417377.1 | c.142A>T | p.Asn48Tyr | missense_variant | 2/2 | 3 | |||
HBD | ENST00000292901.7 | c.316-245A>T | intron_variant | 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: other
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
HEMOGLOBIN A(2) MANZANARES Other:1
other, no assertion criteria provided | literature only | OMIM | Dec 12, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H;H
MutationTaster
Benign
N;N
PrimateAI
Benign
T
Polyphen
P;P;P
Vest4
0.41
MutPred
Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);
MVP
0.93
MPC
0.014
ClinPred
D
GERP RS
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