5-135369490-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_138610.3(MACROH2A1):c.393C>T(p.Pro131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000349 in 1,614,156 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0019 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00019 ( 2 hom. )
Consequence
MACROH2A1
NM_138610.3 synonymous
NM_138610.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0190
Genes affected
MACROH2A1 (HGNC:4740): (macroH2A.1 histone) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene encodes a replication-independent histone that is a member of the histone H2A family. It replaces conventional H2A histones in a subset of nucleosomes where it represses transcription and participates in stable X chromosome inactivation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 5-135369490-G-A is Benign according to our data. Variant chr5-135369490-G-A is described in ClinVar as [Benign]. Clinvar id is 730304.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.019 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MACROH2A1 | NM_138610.3 | c.393C>T | p.Pro131= | synonymous_variant | 4/9 | ENST00000511689.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MACROH2A1 | ENST00000511689.6 | c.393C>T | p.Pro131= | synonymous_variant | 4/9 | 1 | NM_138610.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00188 AC: 286AN: 152180Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.000537 AC: 135AN: 251486Hom.: 1 AF XY: 0.000405 AC XY: 55AN XY: 135912
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GnomAD4 exome AF: 0.000189 AC: 276AN: 1461858Hom.: 2 Cov.: 32 AF XY: 0.000157 AC XY: 114AN XY: 727230
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GnomAD4 genome AF: 0.00188 AC: 287AN: 152298Hom.: 2 Cov.: 33 AF XY: 0.00183 AC XY: 136AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 26, 2018 | - - |
Computational scores
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Benign
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Benign
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Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at