rs41404150
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_000559.3(HBG1):c.110C>G(p.Pro37Arg) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. 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: 6)
Exomes 𝑓: 0.0000025 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HBG1
NM_000559.3 missense
NM_000559.3 missense
Scores
10
5
2
Clinical Significance
Conservation
PhyloP100: 7.48
Genes affected
HBG1 (HGNC:4831): (hemoglobin subunit gamma 1) The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5'-epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.94
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBG1 | NM_000559.3 | c.110C>G | p.Pro37Arg | missense_variant | 2/3 | ENST00000330597.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBG1 | ENST00000330597.5 | c.110C>G | p.Pro37Arg | missense_variant | 2/3 | 1 | NM_000559.3 | P1 | |
HBG1 | ENST00000632727.1 | c.72C>G | p.Pro24= | synonymous_variant | 2/3 | 3 | |||
HBG1 | ENST00000648735.1 | n.161C>G | non_coding_transcript_exon_variant | 2/2 |
Frequencies
GnomAD3 genomes ? Cov.: 6
GnomAD3 genomes
?
Cov.:
6
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000253 AC: 2AN: 791328Hom.: 0 Cov.: 11 AF XY: 0.00000248 AC XY: 1AN XY: 403088
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
2
AN:
791328
Hom.:
Cov.:
11
AF XY:
AC XY:
1
AN XY:
403088
Gnomad4 AFR exome
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Gnomad4 SAS exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 6
GnomAD4 genome
?
Cov.:
6
ClinVar
Significance: other
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
HEMOGLOBIN F (PENDERGRASS) Other:1
other, no assertion criteria provided | literature only | OMIM | Jul 15, 2011 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 5e-04);
MVP
MPC
ClinPred
D
GERP RS
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