chr7-23254235-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1
The NM_002510.3(GPNMB):c.290C>T(p.Ala97Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,613,444 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00034 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 2 hom. )
Consequence
GPNMB
NM_002510.3 missense
NM_002510.3 missense
Scores
17
Clinical Significance
Conservation
PhyloP100: 0.159
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0036859512).
BP6
?
Variant 7-23254235-C-T is Benign according to our data. Variant chr7-23254235-C-T is described in ClinVar as [Benign]. Clinvar id is 746646.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000341 (52/152272) while in subpopulation EAS AF= 0.00907 (47/5180). AF 95% confidence interval is 0.00701. There are 1 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPNMB | NM_002510.3 | c.290C>T | p.Ala97Val | missense_variant | 3/11 | ENST00000258733.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPNMB | ENST00000258733.9 | c.290C>T | p.Ala97Val | missense_variant | 3/11 | 1 | NM_002510.3 |
Frequencies
GnomAD3 genomes ? AF: 0.000335 AC: 51AN: 152154Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000656 AC: 165AN: 251374Hom.: 1 AF XY: 0.000618 AC XY: 84AN XY: 135850
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GnomAD4 exome AF: 0.000149 AC: 218AN: 1461172Hom.: 2 Cov.: 30 AF XY: 0.000142 AC XY: 103AN XY: 726966
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GnomAD4 genome ? AF: 0.000341 AC: 52AN: 152272Hom.: 1 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74454
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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 | Invitae | Sep 19, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;.
REVEL
Benign
Sift
Benign
T;T;T;.
Sift4G
Benign
T;T;T;.
Polyphen
B;B;B;.
Vest4
MVP
MPC
0.071
ClinPred
T
GERP RS
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gMVP
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