rs2292883

Positions:

• chr2-237534357-C-T

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.1021-207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,180 control chromosomes in the GnomAD database, including 973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (973 hom., cov: 32)
• Consequence: MLPH NM_024101.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94

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=-0.92).
• BP6: Variant 2-237534357-C-T is Benign according to our data. Variant chr2-237534357-C-T is described in ClinVar as [Benign]. Clinvar id is 1288073.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLPH	NM_024101.7	c.1021-207C>T		intron_variant		ENST00000264605.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLPH	ENST00000264605.8	c.1021-207C>T		intron_variant		1	NM_024101.7	A2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15719 AN: 152062 Hom.: 967 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0553

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.103 AC: 15741 AN: 152180 Hom.: 973 Cov.: 32 AF XY: 0.106 AC XY: 7861 AN XY: 74400

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.0553

Gnomad4 NFE AF: 0.0789

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0922 Hom.: 352

Bravo AF: 0.110

Asia WGS AF: 0.191 AC: 665 AN: 3478

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	-0.92
CADD	Benign	0.23
DANN	Benign	0.52

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: rs2292883; hg19: chr2-238443000; COSMIC: COSV52823691;