rs1343768

Variant names:

• chr2-237536238-G-A
• rs1343768
• NM_024101.7:c.1104+1591G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024101.7(MLPH):​c.1104+1591G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,892 control chromosomes in the GnomAD database, including 3,624 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3624 hom., cov: 32)
• Consequence: MLPH NM_024101.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• Griscelli syndrome type 3

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLPH	NM_024101.7	c.1104+1591G>A		intron_variant	Intron 9 of 15	ENST00000264605.8	NP_077006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLPH	ENST00000264605.8	c.1104+1591G>A		intron_variant	Intron 9 of 15	1	NM_024101.7	ENSP00000264605.3

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30129 AN: 151770 Hom.: 3615 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0624

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.181

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30173 AN: 151892 Hom.: 3624 Cov.: 32 AF XY: 0.195 AC XY: 14439 AN XY: 74230

African (AFR) AF: 0.332 AC: 13770 AN: 41416

American (AMR) AF: 0.115 AC: 1758 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3470

East Asian (EAS) AF: 0.0622 AC: 320 AN: 5148

South Asian (SAS) AF: 0.129 AC: 616 AN: 4776

European-Finnish (FIN) AF: 0.136 AC: 1439 AN: 10564

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11245 AN: 67942

Other (OTH) AF: 0.178 AC: 375 AN: 2110

Alfa AF: 0.189 Hom.: 600

Bravo AF: 0.203

Asia WGS AF: 0.100 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.98
DANN	Benign	0.44
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1343768; hg19: chr2-238444881;