chr17-45439688-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_014798.3(PLEKHM1):c.2902-54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,609,230 control chromosomes in the GnomAD database, including 22,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.12 ( 1527 hom., cov: 33)
Exomes 𝑓: 0.16 ( 21159 hom. )
Consequence
PLEKHM1
NM_014798.3 intron
NM_014798.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.695
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 17-45439688-G-A is Benign according to our data. Variant chr17-45439688-G-A is described in ClinVar as [Benign]. Clinvar id is 1258903.Status of the report is criteria_provided_single_submitter, 1 stars.
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 | UniProt |
---|---|---|---|---|---|---|---|
PLEKHM1 | NM_014798.3 | c.2902-54C>T | intron_variant | ENST00000430334.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHM1 | ENST00000430334.8 | c.2902-54C>T | intron_variant | 1 | NM_014798.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.120 AC: 18242AN: 152128Hom.: 1529 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
18242
AN:
152128
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.122 AC: 30239AN: 247296Hom.: 2504 AF XY: 0.126 AC XY: 16860AN XY: 134002
GnomAD3 exomes
AF:
AC:
30239
AN:
247296
Hom.:
AF XY:
AC XY:
16860
AN XY:
134002
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.160 AC: 233266AN: 1456984Hom.: 21159 Cov.: 31 AF XY: 0.158 AC XY: 114813AN XY: 724914
GnomAD4 exome
AF:
AC:
233266
AN:
1456984
Hom.:
Cov.:
31
AF XY:
AC XY:
114813
AN XY:
724914
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.120 AC: 18232AN: 152246Hom.: 1527 Cov.: 33 AF XY: 0.112 AC XY: 8347AN XY: 74426
GnomAD4 genome
?
AF:
AC:
18232
AN:
152246
Hom.:
Cov.:
33
AF XY:
AC XY:
8347
AN XY:
74426
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
93
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at