chr1-110060790-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_006492.3(ALX3):c.975C>T(p.Leu325=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,613,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000079 ( 0 hom. )
Consequence
ALX3
NM_006492.3 synonymous
NM_006492.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.480
Genes affected
ALX3 (HGNC:449): (ALX homeobox 3) This gene encodes a nuclear protein with a homeobox DNA-binding domain that functions as a transcriptional regulator involved in cell-type differentiation and development. Preferential methylation of this gene's promoter is associated with advanced-stage neuroblastoma tumors. [provided by RefSeq, Jul 2008]
STRIP1 (HGNC:25916): (striatin interacting protein 1) This gene encodes a member of the striatin-interacting phosphatase and kinase complex, which is involved in localization of the Golgi body. The encoded protein participates in cytosketelal organization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 1-110060790-G-A is Benign according to our data. Variant chr1-110060790-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3043120.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.48 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000854 (13/152312) while in subpopulation SAS AF= 0.00145 (7/4826). AF 95% confidence interval is 0.00068. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALX3 | NM_006492.3 | c.975C>T | p.Leu325= | synonymous_variant | 4/4 | ENST00000647563.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALX3 | ENST00000647563.2 | c.975C>T | p.Leu325= | synonymous_variant | 4/4 | NM_006492.3 | P1 | ||
ENST00000554749.1 | n.2451G>A | non_coding_transcript_exon_variant | 1/1 | ||||||
ALX3 | ENST00000649954.1 | c.546C>T | p.Leu182= | synonymous_variant | 3/3 | ||||
STRIP1 | ENST00000473429.5 | n.4213+5988G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152194Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000216 AC: 54AN: 250524Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135436
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GnomAD4 exome AF: 0.0000787 AC: 115AN: 1461066Hom.: 0 Cov.: 34 AF XY: 0.0000881 AC XY: 64AN XY: 726726
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ALX3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 28, 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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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at