17-45439036-A-G

Position:

• chr17-45439036-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014798.3(PLEKHM1):​c.3059+441T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,320 control chromosomes in the GnomAD database, including 1,529 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 0.12 (1529 hom., cov: 32)
• Consequence: PLEKHM1 NM_014798.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370

Genes affected

PLEKHM1 (HGNC:29017): (pleckstrin homology and RUN domain containing M1) The protein encoded by this gene is essential for bone resorption, and may play a critical role in vesicular transport in the osteoclast. Mutations in this gene are associated with autosomal recessive osteopetrosis type 6 (OPTB6). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]

PLEKHM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHM1	NM_014798.3	c.3059+441T>C		intron_variant		ENST00000430334.8	NP_055613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHM1	ENST00000430334.8	c.3059+441T>C		intron_variant		1	NM_014798.3	ENSP00000389913.3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18271 AN: 152202 Hom.: 1531 Cov.: 32

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0598

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.120 AC: 18261 AN: 152320 Hom.: 1529 Cov.: 32 AF XY: 0.112 AC XY: 8359 AN XY: 74480

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0599

Gnomad4 FIN AF: 0.0417

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.162

Alfa AF: 0.161 Hom.: 564

Bravo AF: 0.127

Asia WGS AF: 0.0260 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	16
DANN	Benign	0.91

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: rs17631303; hg19: chr17-43516402;