NM_015164.4:c.-40_-35dupCGGCGG

Variant names:

• chr1-15684510-G-GGGCGGC
• rs767880122
• NM_015164.4:c.-40_-35dupCGGCGG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_015164.4(PLEKHM2):​c.-40_-35dupCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000060 (1 hom.)
• Consequence: PLEKHM2 NM_015164.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

Genes affected

PLEKHM2 (HGNC:29131): (pleckstrin homology and RUN domain containing M2) This gene encodes a protein that binds the plus-end directed microtubule motor protein kinesin, together with the lysosomal GTPase Arl8, and is required for lysosomes to distribute away from the microtubule-organizing center. The encoded protein belongs to the multisubunit BLOC-one-related complex that regulates lysosome positioning. It binds a Salmonella effector protein called Salmonella induced filament A and is a critical host determinant in Salmonella pathogenesis. It has a domain architecture consisting of an N-terminal RPIP8, UNC-14, and NESCA (RUN) domain that binds kinesin-1 as well as the lysosomal GTPase Arl8, and a C-terminal pleckstrin homology domain that binds the Salmonella induced filament A effector protein. Naturally occurring mutations in this gene lead to abnormal localization of lysosomes, impaired autophagy flux and are associated with recessive dilated cardiomyopathy and left ventricular noncompaction. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHM2	NM_015164.4	c.-40_-35dupCGGCGG		5_prime_UTR_variant	Exon 1 of 20	ENST00000375799.8	NP_055979.2
PLEKHM2	NM_001410755.1	c.-40_-35dupCGGCGG		5_prime_UTR_variant	Exon 1 of 19		NP_001397684.1
PLEKHM2	XM_017000757.1	c.99+2820_99+2825dupCGGCGG		intron_variant	Intron 1 of 19		XP_016856246.1
PLEKHM2	XM_017000758.1	c.99+2820_99+2825dupCGGCGG		intron_variant	Intron 1 of 18		XP_016856247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHM2	ENST00000375799	c.-40_-35dupCGGCGG		5_prime_UTR_variant	Exon 1 of 20	1	NM_015164.4	ENSP00000364956.3
PLEKHM2	ENST00000375793	c.-40_-35dupCGGCGG		5_prime_UTR_variant	Exon 1 of 19	5		ENSP00000364950.2
PLEKHM2	ENST00000642363.1	c.-49_-48insGGCGGC		upstream_gene_variant				ENSP00000494591.1
PLEKHM2	ENST00000462455.1	n.-31_-30insGGCGGC		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 18 AN: 144044 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000341

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.000138

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000600 AC: 50 AN: 832698 Hom.: 1 Cov.: 17 AF XY: 0.0000768 AC XY: 30 AN XY: 390528

Gnomad4 AFR exome AF: 0.0000654

Gnomad4 AMR exome AF: 0.000390

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000640

Gnomad4 OTH exome AF: 0.0000354

GnomAD4 genome AF: 0.000118 AC: 17 AN: 144100 Hom.: 0 Cov.: 0 AF XY: 0.000100 AC XY: 7 AN XY: 70004

Gnomad4 AFR AF: 0.0000746

Gnomad4 AMR AF: 0.000341

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000123

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs767880122; hg19: chr1-16011005;