18-8706488-G-A
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_001395333.1(MTCL1):c.828G>A(p.Ala276Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 1,269,540 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.015 ( 35 hom., cov: 33)
Exomes 𝑓: 0.020 ( 271 hom. )
Consequence
MTCL1
NM_001395333.1 synonymous
NM_001395333.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0320
Genes affected
MTCL1 (HGNC:29121): (microtubule crosslinking factor 1) Enables microtubule binding activity. Predicted to be involved in establishment or maintenance of epithelial cell apical/basal polarity; microtubule bundle formation; and positive regulation of protein targeting to membrane. Located in midbody and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 18-8706488-G-A is Benign according to our data. Variant chr18-8706488-G-A is described in ClinVar as [Benign]. Clinvar id is 3068677.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.032 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0153 (2320/151974) while in subpopulation SAS AF= 0.029 (140/4822). AF 95% confidence interval is 0.0251. There are 35 homozygotes in gnomad4. There are 1166 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 35 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MTCL1 | NM_001395333.1 | c.828G>A | p.Ala276Ala | synonymous_variant | 1/15 | ENST00000695636.1 | NP_001382262.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MTCL1 | ENST00000695636.1 | c.828G>A | p.Ala276Ala | synonymous_variant | 1/15 | NM_001395333.1 | ENSP00000512073.1 | |||
MTCL1 | ENST00000695635.1 | c.828G>A | p.Ala276Ala | synonymous_variant | 1/14 | ENSP00000512072.1 | ||||
MTCL1 | ENST00000306329.16 | c.828G>A | p.Ala276Ala | synonymous_variant | 1/15 | 5 | ENSP00000305027.11 | |||
GACAT2 | ENST00000579368.2 | n.630+582C>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0153 AC: 2319AN: 151868Hom.: 34 Cov.: 33
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GnomAD3 exomes AF: 0.0275 AC: 15AN: 546Hom.: 0 AF XY: 0.0242 AC XY: 8AN XY: 330
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GnomAD4 exome AF: 0.0198 AC: 22129AN: 1117566Hom.: 271 Cov.: 36 AF XY: 0.0202 AC XY: 10743AN XY: 531770
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GnomAD4 genome AF: 0.0153 AC: 2320AN: 151974Hom.: 35 Cov.: 33 AF XY: 0.0157 AC XY: 1166AN XY: 74312
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cerebellar ataxia Benign:1
Benign, criteria provided, single submitter | clinical testing | Molecular Genetics, Royal Melbourne Hospital | May 04, 2023 | European Non-Finnish population allele frequency is 1.223% (rs151052217, 239/15674 alleles, 1 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as BENIGN. Following criteria are met: BA1 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at