chr7-23256953-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_002510.3(GPNMB):c.429C>T(p.Asp143=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 1,613,802 control chromosomes in the GnomAD database, including 1,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.043 ( 209 hom., cov: 33)
Exomes 𝑓: 0.033 ( 1334 hom. )
Consequence
GPNMB
NM_002510.3 synonymous
NM_002510.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.771
Genes affected
GPNMB (HGNC:4462): (glycoprotein nmb) The protein encoded by this gene is a type I transmembrane glycoprotein which shows homology to the pMEL17 precursor, a melanocyte-specific protein. GPNMB shows expression in the lowly metastatic human melanoma cell lines and xenografts but does not show expression in the highly metastatic cell lines. GPNMB may be involved in growth delay and reduction of metastatic potential. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 7-23256953-C-T is Benign according to our data. Variant chr7-23256953-C-T is described in ClinVar as [Benign]. Clinvar id is 3055318.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.771 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0912 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPNMB | NM_002510.3 | c.429C>T | p.Asp143= | synonymous_variant | 4/11 | ENST00000258733.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPNMB | ENST00000258733.9 | c.429C>T | p.Asp143= | synonymous_variant | 4/11 | 1 | NM_002510.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0428 AC: 6508AN: 152120Hom.: 209 Cov.: 33
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GnomAD3 exomes AF: 0.0465 AC: 11681AN: 251456Hom.: 397 AF XY: 0.0493 AC XY: 6695AN XY: 135904
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GnomAD4 exome AF: 0.0329 AC: 48020AN: 1461564Hom.: 1334 Cov.: 32 AF XY: 0.0348 AC XY: 25326AN XY: 727102
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GnomAD4 genome ? AF: 0.0428 AC: 6523AN: 152238Hom.: 209 Cov.: 33 AF XY: 0.0473 AC XY: 3519AN XY: 74420
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
GPNMB-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 28, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at