chr2-237510678-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_024101.7(MLPH):c.215A>G(p.Gln72Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00697 in 1,613,788 control chromosomes in the GnomAD database, including 285 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0087 ( 21 hom., cov: 33)
Exomes 𝑓: 0.0068 ( 264 hom. )
Consequence
MLPH
NM_024101.7 missense
NM_024101.7 missense
Scores
17
Clinical Significance
Conservation
PhyloP100: 3.06
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.00254789).
BP6
?
Variant 2-237510678-A-G is Benign according to our data. Variant chr2-237510678-A-G is described in ClinVar as [Benign]. Clinvar id is 1599849.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MLPH | NM_024101.7 | c.215A>G | p.Gln72Arg | missense_variant | 3/16 | ENST00000264605.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MLPH | ENST00000264605.8 | c.215A>G | p.Gln72Arg | missense_variant | 3/16 | 1 | NM_024101.7 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00868 AC: 1321AN: 152226Hom.: 20 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0167 AC: 4201AN: 251198Hom.: 96 AF XY: 0.0177 AC XY: 2401AN XY: 135876
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GnomAD4 exome AF: 0.00680 AC: 9932AN: 1461444Hom.: 264 Cov.: 31 AF XY: 0.00802 AC XY: 5827AN XY: 727004
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GnomAD4 genome ? AF: 0.00868 AC: 1323AN: 152344Hom.: 21 Cov.: 33 AF XY: 0.0108 AC XY: 808AN XY: 74494
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ExAC
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.0
.;.;B;B;.
Vest4
0.062, 0.064, 0.081, 0.080
MPC
0.11
ClinPred
T
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at