chr7-27173638-G-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The ENST00000283921.5(HOXA10):c.669C>T(p.Ala223=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00343 in 1,544,924 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.0057 ( 25 hom., cov: 33)
Exomes 𝑓: 0.0032 ( 94 hom. )
Consequence
HOXA10
ENST00000283921.5 synonymous
ENST00000283921.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.69
Genes affected
HOXA10 (HGNC:5100): (homeobox A10) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor that may regulate gene expression, morphogenesis, and differentiation. More specifically, it may function in fertility, embryo viability, and regulation of hematopoietic lineage commitment. Alternatively spliced transcript variants have been described. Read-through transcription also exists between this gene and the downstream homeobox A9 (HOXA9) gene. [provided by RefSeq, Mar 2011]
HOXA9 (HGNC:5109): (homeobox A9) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. This gene is highly similar to the abdominal-B (Abd-B) gene of Drosophila. A specific translocation event which causes a fusion between this gene and the NUP98 gene has been associated with myeloid leukemogenesis. Read-through transcription exists between this gene and the upstream homeobox A10 (HOXA10) gene.[provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 7-27173638-G-A is Benign according to our data. Variant chr7-27173638-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3052831.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAd4 at 865 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HOXA10 | NM_018951.4 | c.669C>T | p.Ala223= | synonymous_variant | 1/2 | ENST00000283921.5 | NP_061824.3 | |
HOXA10-HOXA9 | NR_037940.1 | n.616+6008C>T | intron_variant, non_coding_transcript_variant | |||||
HOXA10 | NR_037939.2 | n.217-1465C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HOXA10 | ENST00000283921.5 | c.669C>T | p.Ala223= | synonymous_variant | 1/2 | 1 | NM_018951.4 | ENSP00000283921 | P2 | |
HOXA10 | ENST00000396344.4 | c.11-1465C>T | intron_variant | 1 | ENSP00000379633 | A1 | ||||
HOXA9 | ENST00000465941.1 | n.479+1064C>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.00569 AC: 865AN: 152028Hom.: 25 Cov.: 33
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GnomAD3 exomes AF: 0.00779 AC: 1102AN: 141498Hom.: 39 AF XY: 0.00701 AC XY: 537AN XY: 76632
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GnomAD4 exome AF: 0.00318 AC: 4428AN: 1392786Hom.: 94 Cov.: 33 AF XY: 0.00302 AC XY: 2072AN XY: 686804
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GnomAD4 genome AF: 0.00569 AC: 865AN: 152138Hom.: 25 Cov.: 33 AF XY: 0.00817 AC XY: 608AN XY: 74394
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | HOXA10: BP4, BS2 - |
HOXA10-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 13, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Benign
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at