chr17-45464290-C-T

Variant names:

• chr17-45464290-C-T
• rs3946526
• NM_014798.3:c.1308+3919G>A

Variant summary

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

The NM_014798.3(PLEKHM1):​c.1308+3919G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,186 control chromosomes in the GnomAD database, including 1,550 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 (1550 hom., cov: 32)
• Consequence: PLEKHM1 NM_014798.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167

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]

ENSG00000236234 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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 rank	MANE	Protein	UniProt
PLEKHM1	NM_014798.3	c.1308+3919G>A		intron_variant	Intron 5 of 11	ENST00000430334.8	NP_055613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHM1	ENST00000430334.8	c.1308+3919G>A		intron_variant	Intron 5 of 11	1	NM_014798.3	ENSP00000389913.3

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18732 AN: 152068 Hom.: 1552 Cov.: 32

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0596

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.123 AC: 18722 AN: 152186 Hom.: 1550 Cov.: 32 AF XY: 0.115 AC XY: 8579 AN XY: 74402

Gnomad4 AFR AF: 0.0433

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0594

Gnomad4 FIN AF: 0.0417

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.167

Alfa AF: 0.135 Hom.: 253

Bravo AF: 0.130

Asia WGS AF: 0.0260 AC: 92 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.25

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: rs3946526; hg19: chr17-43541656;