chr2-237518551-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024101.7(MLPH):c.458T>C(p.Leu153Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,611,472 control chromosomes in the GnomAD database, including 24,326 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3729 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20597 hom. )

Consequence

MLPH
NM_024101.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.671

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]

MLPH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018135309).

BP6

Variant 2-237518551-T-C is Benign according to our data. Variant chr2-237518551-T-C is described in ClinVar as [Benign]. Clinvar id is 1267164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLPH	NM_024101.7 link	c.458T>C	p.Leu153Pro	missense_variant	Exon 5 of 16	ENST00000264605.8	NP_077006.1	Q9BV36-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLPH	ENST00000264605.8 link	c.458T>C	p.Leu153Pro	missense_variant	Exon 5 of 16	1	NM_024101.7	ENSP00000264605.3		Q9BV36-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30399

AN:

151866

Hom.:

3715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.341

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.0726

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.145

AC:

36068

AN:

248958

Hom.:

3152

AF XY:

0.142

AC XY:

19182

AN XY:

134752

show subpopulations

Gnomad AFR exome

AF:

0.343

Gnomad AMR exome

AF:

0.0718

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.0676

Gnomad SAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.162

AC:

236876

AN:

1459486

Hom.:

20597

Cov.:

AF XY:

0.161

AC XY:

116931

AN XY:

726030

show subpopulations

Gnomad4 AFR exome

AF:

0.348

Gnomad4 AMR exome

AF:

0.0770

Gnomad4 ASJ exome

AF:

0.132

Gnomad4 EAS exome

AF:

0.0675

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.200

AC:

30448

AN:

151986

Hom.:

3729

Cov.:

AF XY:

0.196

AC XY:

14588

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.342

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.0724

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.165

Gnomad4 OTH

AF:

0.171

Alfa

AF:

0.164

Hom.:

4837

Bravo

AF:

0.205

TwinsUK

AF:

0.167

AC:

618

ALSPAC

AF:

0.176

AC:

678

ESP6500AA

AF:

0.346

AC:

1523

ESP6500EA

AF:

0.169

AC:

1456

ExAC

AF:

0.151

AC:

18298

Asia WGS

AF:

0.106

AC:

370

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.64

DANN

Benign

0.20

DEOGEN2

Benign

0.077

.;T;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0051

LIST_S2

Benign

0.13

T;T;T;T

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.2

N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.080

N;N;N;N

REVEL

Benign

0.071

Sift

Benign

0.48

T;T;T;T

Sift4G

Benign

0.23

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.019

MPC

0.17

ClinPred

0.00041

GERP RS

-2.8

Varity_R

0.040

gMVP

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over