2-85357256-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001135022.2(ELMOD3):c.54+4A>C variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00000442 in 1,582,134 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
ELMOD3
NM_001135022.2 splice_donor_region, intron
NM_001135022.2 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.1715
2
Clinical Significance
Conservation
PhyloP100: 4.15
Genes affected
ELMOD3 (HGNC:26158): (ELMO domain containing 3) This gene encodes a member of the engulfment and cell motility family of GTPase-activating proteins that regulate Arf GTPase proteins. Members of this family are defined by a conserved engulfment and cell motility domain. In rat cochlea, the encoded protein is found in stereocilia, kinocilia and cuticular plate of developing hair cells suggesting a function for this protein in cochlear sensory cells. An allelic variant of this family has been associated with autosomal recessive nonsyndromic deafness-88 in humans. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELMOD3 | NM_001135022.2 | c.54+4A>C | splice_donor_region_variant, intron_variant | ENST00000409013.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELMOD3 | ENST00000409013.8 | c.54+4A>C | splice_donor_region_variant, intron_variant | 1 | NM_001135022.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152246Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000814 AC: 2AN: 245768Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133152
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GnomAD4 exome AF: 0.00000280 AC: 4AN: 1429888Hom.: 0 Cov.: 24 AF XY: 0.00000421 AC XY: 3AN XY: 713358
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74386
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1427664). This variant has not been reported in the literature in individuals affected with ELMOD3-related conditions. This variant is present in population databases (rs759029330, gnomAD 0.002%). This sequence change falls in intron 5 of the ELMOD3 gene. It does not directly change the encoded amino acid sequence of the ELMOD3 protein. It affects a nucleotide within the consensus splice site. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -4
Find out detailed SpliceAI scores and Pangolin per-transcript scores at