14-50533475-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001127713.1(ATL1):c.-140+108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,032 control chromosomes in the GnomAD database, including 3,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.20 ( 3868 hom., cov: 32)
Exomes 𝑓: 0.17 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ATL1
NM_001127713.1 intron
NM_001127713.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0290
Genes affected
ATL1 (HGNC:11231): (atlastin GTPase 1) The protein encoded by this gene is a GTPase and a Golgi body transmembrane protein. The encoded protein can form a homotetramer and has been shown to interact with spastin and with mitogen-activated protein kinase kinase kinase kinase 4. This protein may be involved in axonal maintenance as evidenced by the fact that defects in this gene are a cause of spastic paraplegia type 3. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
MAP4K5 (HGNC:6867): (mitogen-activated protein kinase kinase kinase kinase 5) This gene encodes a member of the serine/threonine protein kinase family, that is highly similar to yeast SPS1/STE20 kinase. Yeast SPS1/STE20 functions near the beginning of the MAP kinase signal cascades that is essential for yeast pheromone response. This kinase was shown to activate Jun kinase in mammalian cells, which suggested a role in stress response. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 14-50533475-C-T is Benign according to our data. Variant chr14-50533475-C-T is described in ClinVar as [Benign]. Clinvar id is 1262528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATL1 | NM_001127713.1 | c.-140+108C>T | intron_variant | NP_001121185.1 | ||||
MAP4K5 | XM_047430893.1 | c.-109-1317G>A | intron_variant | XP_047286849.1 | ||||
MAP4K5 | XM_047430897.1 | c.-109-1317G>A | intron_variant | XP_047286853.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATL1 | ENST00000441560.6 | c.-140+108C>T | intron_variant | 1 | ENSP00000413675.2 | |||||
ATL1 | ENST00000556478.3 | c.-140+602C>T | intron_variant | 2 | ENSP00000501428.2 | |||||
MAP4K5 | ENST00000555216.5 | c.-94+9024G>A | intron_variant | 4 | ENSP00000452289.1 | |||||
ATL1 | ENST00000682219.1 | n.740+108C>T | intron_variant |
Frequencies
GnomAD3 genomes AF: 0.202 AC: 30693AN: 151914Hom.: 3868 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.167 AC: 1AN: 6Hom.: 0 AF XY: 0.167 AC XY: 1AN XY: 6
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GnomAD4 genome AF: 0.202 AC: 30700AN: 152032Hom.: 3868 Cov.: 32 AF XY: 0.201 AC XY: 14907AN XY: 74280
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 23, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at