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GeneBe

2-237510643-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_024101.7(MLPH):c.180C>T(p.Asn60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00672 in 1,613,750 control chromosomes in the GnomAD database, including 278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 18 hom., cov: 33)
Exomes 𝑓: 0.0067 ( 260 hom. )

Consequence

MLPH
NM_024101.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.84
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 -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-237510643-C-T is Benign according to our data. Variant chr2-237510643-C-T is described in ClinVar as [Benign]. Clinvar id is 1655837.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.84 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MLPHNM_024101.7 linkuse as main transcriptc.180C>T p.Asn60= synonymous_variant 3/16 ENST00000264605.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MLPHENST00000264605.8 linkuse as main transcriptc.180C>T p.Asn60= synonymous_variant 3/161 NM_024101.7 A2Q9BV36-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00734
AC:
1117
AN:
152214
Hom.:
17
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00429
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0149
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0245
Gnomad SAS
AF:
0.0497
Gnomad FIN
AF:
0.0256
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000897
Gnomad OTH
AF:
0.00525
GnomAD3 exomes
AF:
0.0164
AC:
4112
AN:
251178
Hom.:
92
AF XY:
0.0174
AC XY:
2361
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.00425
Gnomad AMR exome
AF:
0.0302
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0275
Gnomad SAS exome
AF:
0.0565
Gnomad FIN exome
AF:
0.0235
Gnomad NFE exome
AF:
0.00148
Gnomad OTH exome
AF:
0.0140
GnomAD4 exome
AF:
0.00666
AC:
9734
AN:
1461418
Hom.:
260
Cov.:
31
AF XY:
0.00788
AC XY:
5732
AN XY:
727012
show subpopulations
Gnomad4 AFR exome
AF:
0.00373
Gnomad4 AMR exome
AF:
0.0291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0326
Gnomad4 SAS exome
AF:
0.0537
Gnomad4 FIN exome
AF:
0.0235
Gnomad4 NFE exome
AF:
0.000551
Gnomad4 OTH exome
AF:
0.00844
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00734
AC:
1118
AN:
152332
Hom.:
18
Cov.:
33
AF XY:
0.00941
AC XY:
701
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.00428
Gnomad4 AMR
AF:
0.0149
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0245
Gnomad4 SAS
AF:
0.0500
Gnomad4 FIN
AF:
0.0256
Gnomad4 NFE
AF:
0.000897
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00260
Hom.:
3
Bravo
AF:
0.00625
Asia WGS
AF:
0.0440
AC:
151
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000356

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 testingInvitaeJan 08, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
7.4
Dann
Benign
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs2292878; hg19: chr2-238419286; COSMIC: COSV52820024; COSMIC: COSV52820024; API