rs743119
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000370238.8(GCLM):c.-23G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,229,094 control chromosomes in the GnomAD database, including 25,370 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.26 ( 6645 hom., cov: 32)
Exomes 𝑓: 0.18 ( 18725 hom. )
Consequence
GCLM
ENST00000370238.8 5_prime_UTR
ENST00000370238.8 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.205
Genes affected
GCLM (HGNC:4312): (glutamate-cysteine ligase modifier subunit) Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase, is the first rate limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. Gamma glutamylcysteine synthetase deficiency has been implicated in some forms of hemolytic anemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GCLM | NM_002061.4 | c.-23G>T | 5_prime_UTR_variant | 1/7 | ENST00000370238.8 | NP_002052.1 | ||
GCLM | NM_001308253.2 | c.-23G>T | 5_prime_UTR_variant | 1/6 | NP_001295182.1 | |||
GCLM | XM_047418031.1 | c.-23G>T | 5_prime_UTR_variant | 1/7 | XP_047273987.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GCLM | ENST00000370238.8 | c.-23G>T | 5_prime_UTR_variant | 1/7 | 1 | NM_002061.4 | ENSP00000359258 | P1 | ||
GCLM | ENST00000615724.1 | c.-23G>T | 5_prime_UTR_variant | 1/6 | 1 | ENSP00000484507 |
Frequencies
GnomAD3 genomes AF: 0.262 AC: 39501AN: 151002Hom.: 6624 Cov.: 32
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GnomAD3 exomes AF: 0.351 AC: 1082AN: 3082Hom.: 206 AF XY: 0.323 AC XY: 683AN XY: 2116
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GnomAD4 exome AF: 0.178 AC: 191889AN: 1077982Hom.: 18725 Cov.: 31 AF XY: 0.176 AC XY: 91293AN XY: 517260
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GnomAD4 genome AF: 0.262 AC: 39560AN: 151112Hom.: 6645 Cov.: 32 AF XY: 0.259 AC XY: 19117AN XY: 73870
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at