chr5-38407128-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_152403.4(EGFLAM):c.1129G>A(p.Gly377Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,613,254 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
EGFLAM
NM_152403.4 missense
NM_152403.4 missense
Scores
10
6
3
Clinical Significance
Conservation
PhyloP100: 9.12
Genes affected
EGFLAM (HGNC:26810): (EGF like, fibronectin type III and laminin G domains) Predicted to enable calcium ion binding activity and glycosaminoglycan binding activity. Predicted to be involved in animal organ morphogenesis and tissue development. Predicted to act upstream of or within extracellular matrix organization; peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan; and positive regulation of cell-substrate adhesion. Part of cell surface. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.82
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGFLAM | NM_152403.4 | c.1129G>A | p.Gly377Ser | missense_variant | 8/22 | ENST00000322350.10 | |
EGFLAM | NM_001205301.2 | c.1129G>A | p.Gly377Ser | missense_variant | 8/23 | ||
EGFLAM | NM_182798.3 | c.427G>A | p.Gly143Ser | missense_variant | 3/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGFLAM | ENST00000322350.10 | c.1129G>A | p.Gly377Ser | missense_variant | 8/22 | 1 | NM_152403.4 | P3 | |
EGFLAM | ENST00000354891.7 | c.1129G>A | p.Gly377Ser | missense_variant | 8/23 | 1 | A2 | ||
EGFLAM | ENST00000397202.6 | c.-364+3237G>A | intron_variant | 1 | |||||
EGFLAM | ENST00000336740.10 | c.427G>A | p.Gly143Ser | missense_variant | 3/17 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000152 AC: 23AN: 151598Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000166 AC: 41AN: 247398Hom.: 0 AF XY: 0.000149 AC XY: 20AN XY: 134074
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GnomAD4 exome AF: 0.000129 AC: 188AN: 1461656Hom.: 1 Cov.: 31 AF XY: 0.000131 AC XY: 95AN XY: 727104
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GnomAD4 genome AF: 0.000152 AC: 23AN: 151598Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74054
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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 | Jul 09, 2021 | The c.1129G>A (p.G377S) alteration is located in exon 8 (coding exon 8) of the EGFLAM gene. This alteration results from a G to A substitution at nucleotide position 1129, causing the glycine (G) at amino acid position 377 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 18
Find out detailed SpliceAI scores and Pangolin per-transcript scores at