chr17-49506475-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_002507.4(NGFR):c.385G>A(p.Glu129Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 1,610,112 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
NGFR
NM_002507.4 missense
NM_002507.4 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 7.05
Genes affected
NGFR (HGNC:7809): (nerve growth factor receptor) Nerve growth factor receptor contains an extracellular domain containing four 40-amino acid repeats with 6 cysteine residues at conserved positions followed by a serine/threonine-rich region, a single transmembrane domain, and a 155-amino acid cytoplasmic domain. The cysteine-rich region contains the nerve growth factor binding domain. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NGFR | NM_002507.4 | c.385G>A | p.Glu129Lys | missense_variant | 3/6 | ENST00000172229.8 | |
NGFR-AS1 | NR_103773.1 | n.403C>T | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NGFR | ENST00000172229.8 | c.385G>A | p.Glu129Lys | missense_variant | 3/6 | 1 | NM_002507.4 | P1 | |
NGFR-AS1 | ENST00000514506.1 | n.403C>T | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
NGFR | ENST00000504201.1 | c.103G>A | p.Glu35Lys | missense_variant | 3/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152110Hom.: 0 Cov.: 31
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000839 AC: 20AN: 238290Hom.: 0 AF XY: 0.000107 AC XY: 14AN XY: 130840
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GnomAD4 exome AF: 0.000138 AC: 201AN: 1458002Hom.: 0 Cov.: 32 AF XY: 0.000131 AC XY: 95AN XY: 725440
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152110Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74298
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 16, 2021 | The c.385G>A (p.E129K) alteration is located in exon 3 (coding exon 3) of the NGFR gene. This alteration results from a G to A substitution at nucleotide position 385, causing the glutamic acid (E) at amino acid position 129 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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