chr2-237511028-T-C
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_024101.7(MLPH):c.372T>C(p.His124=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,613,892 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0013 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 1 hom. )
Consequence
MLPH
NM_024101.7 synonymous
NM_024101.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.559
Genes affected
MLPH (HGNC:29643): (melanophilin) This gene encodes a member of the exophilin subfamily of Rab effector proteins. The protein forms a ternary complex with the small Ras-related GTPase Rab27A in its GTP-bound form and the motor protein myosin Va. A similar protein complex in mouse functions to tether pigment-producing organelles called melanosomes to the actin cytoskeleton in melanocytes, and is required for visible pigmentation in the hair and skin. A mutation in this gene results in Griscelli syndrome type 3, which is characterized by a silver-gray hair color and abnormal pigment distribution in the hair shaft. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]
MIR6811 (HGNC:49944): (microRNA 6811) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant 2-237511028-T-C is Benign according to our data. Variant chr2-237511028-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 733682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.559 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00133 (203/152146) while in subpopulation AFR AF= 0.00448 (186/41514). AF 95% confidence interval is 0.00395. There are 2 homozygotes in gnomad4. There are 105 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MLPH | NM_024101.7 | c.372T>C | p.His124= | synonymous_variant | 4/16 | ENST00000264605.8 | |
MIR6811 | NR_106869.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MLPH | ENST00000264605.8 | c.372T>C | p.His124= | synonymous_variant | 4/16 | 1 | NM_024101.7 | A2 | |
MIR6811 | ENST00000620409.1 | downstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00134 AC: 203AN: 152028Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000402 AC: 101AN: 251292Hom.: 0 AF XY: 0.000309 AC XY: 42AN XY: 135806
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GnomAD4 exome AF: 0.000125 AC: 182AN: 1461746Hom.: 1 Cov.: 33 AF XY: 0.000114 AC XY: 83AN XY: 727150
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 11, 2023 | - - |
MLPH-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 28, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at