4-1814481-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_012318.3(LETM1):c.2163G>A(p.Glu721Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,996 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 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
LETM1
NM_012318.3 synonymous
NM_012318.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0220
Genes affected
LETM1 (HGNC:6556): (leucine zipper and EF-hand containing transmembrane protein 1) This gene encodes a protein that is localized to the inner mitochondrial membrane. The protein functions to maintain the mitochondrial tubular shapes and is required for normal mitochondrial morphology and cellular viability. Mutations in this gene cause Wolf-Hirschhorn syndrome, a complex malformation syndrome caused by the deletion of parts of the distal short arm of chromosome 4. Related pseudogenes have been identified on chromosomes 8, 15 and 19. [provided by RefSeq, Oct 2009]
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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=-0.47).
BP6
Variant 4-1814481-C-T is Benign according to our data. Variant chr4-1814481-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1577921.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.022 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000137 (20/1461736) while in subpopulation AMR AF= 0.000134 (6/44706). AF 95% confidence interval is 0.0000581. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LETM1 | NM_012318.3 | c.2163G>A | p.Glu721Glu | synonymous_variant | Exon 14 of 14 | ENST00000302787.3 | NP_036450.1 | |
LETM1 | XM_006713884.2 | c.2160G>A | p.Glu720Glu | synonymous_variant | Exon 14 of 14 | XP_006713947.1 | ||
LETM1 | XM_047415673.1 | c.1620G>A | p.Glu540Glu | synonymous_variant | Exon 13 of 13 | XP_047271629.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152260Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250652Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135610
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461736Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727154
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152260Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74392
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Oct 14, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at