2-237534764-G-C

Position:

• chr2-237534764-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024101.7(MLPH):​c.1104+117G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 856,520 control chromosomes in the GnomAD database, including 49,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (15299 hom., cov: 32)
  • Exomes 𝑓: 0.30 (34180 hom.)
• Consequence: MLPH NM_024101.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.947

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 2-237534764-G-C is Benign according to our data. Variant chr2-237534764-G-C is described in ClinVar as [Benign]. Clinvar id is 1273815.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLPH	NM_024101.7	c.1104+117G>C		intron_variant		ENST00000264605.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLPH	ENST00000264605.8	c.1104+117G>C		intron_variant		1	NM_024101.7	A2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61089 AN: 151892 Hom.: 15260 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.374

GnomAD4 exome AF: 0.298 AC: 209673 AN: 704512 Hom.: 34180 AF XY: 0.301 AC XY: 113437 AN XY: 376938

Gnomad4 AFR exome AF: 0.712

Gnomad4 AMR exome AF: 0.343

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.320

GnomAD4 genome AF: 0.403 AC: 61188 AN: 152008 Hom.: 15299 Cov.: 32 AF XY: 0.399 AC XY: 29648 AN XY: 74304

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.375

Alfa AF: 0.143 Hom.: 237

Bravo AF: 0.422

Asia WGS AF: 0.434 AC: 1508 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.62
DANN	Benign	0.38

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

Other links and lift over

dbSNP: rs2292885; hg19: chr2-238443407; COSMIC: COSV52825499;