2-237531806-T-G

Variant names:

• chr2-237531806-T-G
• rs11891348
• NM_024101.7:c.1021-2758T>G

Variant summary

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

The NM_024101.7(MLPH):​c.1021-2758T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 151,826 control chromosomes in the GnomAD database, including 4,296 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 0.23 (4296 hom., cov: 32)
• Consequence: MLPH NM_024101.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509
• Publications: 10 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: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024101.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLPH	NM_024101.7	MANE Select	c.1021-2758T>G		intron	N/A	NP_077006.1	Q9BV36-1
	MLPH	NM_001042467.3		c.1020+4290T>G		intron	N/A	NP_001035932.1	Q9BV36-2
	MLPH	NM_001281473.2		c.900+4290T>G		intron	N/A	NP_001268402.1	Q9BV36-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLPH	ENST00000264605.8	TSL:1 MANE Select	c.1021-2758T>G		intron	N/A	ENSP00000264605.3	Q9BV36-1
	MLPH	ENST00000338530.8	TSL:1	c.1020+4290T>G		intron	N/A	ENSP00000341845.4	Q9BV36-2
	MLPH	ENST00000409373.5	TSL:1	c.900+4290T>G		intron	N/A	ENSP00000386780.1	Q9BV36-3

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35605 AN: 151708 Hom.: 4288 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.235 AC: 35635 AN: 151826 Hom.: 4296 Cov.: 32 AF XY: 0.234 AC XY: 17387 AN XY: 74176

African (AFR) AF: 0.200 AC: 8297 AN: 41396

American (AMR) AF: 0.270 AC: 4126 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 769 AN: 3470

East Asian (EAS) AF: 0.295 AC: 1522 AN: 5160

South Asian (SAS) AF: 0.371 AC: 1773 AN: 4778

European-Finnish (FIN) AF: 0.184 AC: 1934 AN: 10522

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16510 AN: 67922

Other (OTH) AF: 0.233 AC: 489 AN: 2098

Alfa AF: 0.238 Hom.: 2243

Bravo AF: 0.237

Asia WGS AF: 0.320 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.47
PhyloP100		-0.51
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: rs11891348; hg19: chr2-238440449;