chr7-23260029-C-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_002510.3(GPNMB):c.591C>T(p.Asn197=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,614,042 control chromosomes in the GnomAD database, including 291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.025 ( 150 hom., cov: 32)
Exomes 𝑓: 0.0052 ( 141 hom. )
Consequence
GPNMB
NM_002510.3 synonymous
NM_002510.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.58
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
?
Variant 7-23260029-C-T is Benign according to our data. Variant chr7-23260029-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 778296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.58 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0783 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPNMB | NM_002510.3 | c.591C>T | p.Asn197= | synonymous_variant | 5/11 | ENST00000258733.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPNMB | ENST00000258733.9 | c.591C>T | p.Asn197= | synonymous_variant | 5/11 | 1 | NM_002510.3 | ||
GPNMB | ENST00000381990.6 | c.591C>T | p.Asn197= | synonymous_variant | 5/11 | 1 | |||
GPNMB | ENST00000647578.1 | c.591C>T | p.Asn197= | synonymous_variant | 5/12 | P1 | |||
GPNMB | ENST00000465673.5 | n.769C>T | non_coding_transcript_exon_variant | 6/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0250 AC: 3805AN: 152148Hom.: 150 Cov.: 32
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GnomAD3 exomes AF: 0.00812 AC: 2042AN: 251456Hom.: 66 AF XY: 0.00658 AC XY: 894AN XY: 135906
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GnomAD4 exome AF: 0.00520 AC: 7606AN: 1461776Hom.: 141 Cov.: 31 AF XY: 0.00486 AC XY: 3531AN XY: 727196
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GnomAD4 genome ? AF: 0.0251 AC: 3815AN: 152266Hom.: 150 Cov.: 32 AF XY: 0.0243 AC XY: 1807AN XY: 74456
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 17, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
GPNMB-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 22, 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
Benign
Dann
Benign
Splicing
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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