rs2292883

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_024101.7(MLPH):​c.1021-207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,180 control chromosomes in the GnomAD database, including 973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 973 hom., cov: 32)

Consequence

MLPH
NM_024101.7 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.94
Variant links:
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 (BayesDel_noAF=-0.92).
BP6
Variant 2-237534357-C-T is Benign according to our data. Variant chr2-237534357-C-T is described in ClinVar as [Benign]. Clinvar id is 1288073.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MLPHNM_024101.7 linkuse as main transcriptc.1021-207C>T intron_variant ENST00000264605.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MLPHENST00000264605.8 linkuse as main transcriptc.1021-207C>T intron_variant 1 NM_024101.7 A2Q9BV36-1

Frequencies

GnomAD3 genomes
AF:
0.103
AC:
15719
AN:
152062
Hom.:
967
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.102
Gnomad AMI
AF:
0.0471
Gnomad AMR
AF:
0.178
Gnomad ASJ
AF:
0.122
Gnomad EAS
AF:
0.209
Gnomad SAS
AF:
0.208
Gnomad FIN
AF:
0.0553
Gnomad MID
AF:
0.123
Gnomad NFE
AF:
0.0789
Gnomad OTH
AF:
0.112
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.103
AC:
15741
AN:
152180
Hom.:
973
Cov.:
32
AF XY:
0.106
AC XY:
7861
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.102
Gnomad4 AMR
AF:
0.178
Gnomad4 ASJ
AF:
0.122
Gnomad4 EAS
AF:
0.209
Gnomad4 SAS
AF:
0.208
Gnomad4 FIN
AF:
0.0553
Gnomad4 NFE
AF:
0.0789
Gnomad4 OTH
AF:
0.117
Alfa
AF:
0.0922
Hom.:
352
Bravo
AF:
0.110
Asia WGS
AF:
0.191
AC:
665
AN:
3478

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 submitterclinical testingGeneDxNov 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.23
DANN
Benign
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2292883; hg19: chr2-238443000; COSMIC: COSV52823691; API