Variant 2-237510643-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

MLPH links:

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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=-0.54).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.84 with no splicing effect.

BA1

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	Protein	UniProt
MLPH	NM_024101.7 linkuse as main transcript	c.180C>T	p.Asn60=	synonymous_variant	3/16	ENST00000264605.8	NP_077006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLPH	ENST00000264605.8 linkuse as main transcript	c.180C>T	p.Asn60=	synonymous_variant	3/16	1	NM_024101.7	ENSP00000264605	A2	Q9BV36-1

Frequencies

GnomAD3 genomes

AF:

0.00734

AC:

1117

AN:

152214

Hom.:

Cov.:

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.:

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.:

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

AF:

0.00734

AC:

1118

AN:

152332

Hom.:

Cov.:

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.:

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 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.

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