rs4696
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_005340.7(HINT1):āc.57T>Cā(p.Phe19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 1,612,466 control chromosomes in the GnomAD database, including 5,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.12 ( 2642 hom., cov: 33)
Exomes š: 0.038 ( 3094 hom. )
Consequence
HINT1
NM_005340.7 synonymous
NM_005340.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.763
Genes affected
HINT1 (HGNC:4912): (histidine triad nucleotide binding protein 1) This gene encodes a protein that hydrolyzes purine nucleotide phosphoramidates substrates, including AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester, and AMP-NH2. The encoded protein interacts with these substrates via a histidine triad motif. This gene is considered a tumor suppressor gene. In addition, mutations in this gene can cause autosomal recessive neuromyotonia and axonal neuropathy. There are several related pseudogenes on chromosome 7. Several transcript variants have been observed. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 5-131165149-A-G is Benign according to our data. Variant chr5-131165149-A-G is described in ClinVar as [Benign]. Clinvar id is 259745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-131165149-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.763 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HINT1 | NM_005340.7 | c.57T>C | p.Phe19= | synonymous_variant | 1/3 | ENST00000304043.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HINT1 | ENST00000304043.10 | c.57T>C | p.Phe19= | synonymous_variant | 1/3 | 1 | NM_005340.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.118 AC: 17954AN: 152146Hom.: 2639 Cov.: 33
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GnomAD3 exomes AF: 0.0504 AC: 12571AN: 249504Hom.: 1144 AF XY: 0.0438 AC XY: 5913AN XY: 135040
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GnomAD4 exome AF: 0.0379 AC: 55399AN: 1460202Hom.: 3094 Cov.: 32 AF XY: 0.0368 AC XY: 26761AN XY: 726506
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GnomAD4 genome AF: 0.118 AC: 17990AN: 152264Hom.: 2642 Cov.: 33 AF XY: 0.114 AC XY: 8462AN XY: 74450
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 06, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Autosomal recessive axonal neuropathy with neuromyotonia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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