12-69348448-G-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000239.3(LYZ):c.40G>T(p.Val14Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
LYZ
NM_000239.3 missense
NM_000239.3 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: -0.0440
Genes affected
LYZ (HGNC:6740): (lysozyme) This gene encodes human lysozyme, whose natural substrate is the bacterial cell wall peptidoglycan (cleaving the beta[1-4]glycosidic linkages between N-acetylmuramic acid and N-acetylglucosamine). Lysozyme is one of the antimicrobial agents found in human milk, and is also present in spleen, lung, kidney, white blood cells, plasma, saliva, and tears. The protein has antibacterial activity against a number of bacterial species. Missense mutations in this gene have been identified in heritable renal amyloidosis. [provided by RefSeq, Oct 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.037285894).
BS2
?
High AC in GnomAdExome at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LYZ | NM_000239.3 | c.40G>T | p.Val14Phe | missense_variant | 1/4 | ENST00000261267.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LYZ | ENST00000261267.7 | c.40G>T | p.Val14Phe | missense_variant | 1/4 | 1 | NM_000239.3 | P1 | |
LYZ | ENST00000549690.1 | c.40G>T | p.Val14Phe | missense_variant | 1/3 | 2 | |||
LYZ | ENST00000548839.1 | c.40G>T | p.Val14Phe | missense_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152182Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251484Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135920
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727244
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74474
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 26, 2022 | The c.40G>T (p.V14F) alteration is located in exon 1 (coding exon 1) of the LYZ gene. This alteration results from a G to T substitution at nucleotide position 40, causing the valine (V) at amino acid position 14 to be replaced by a phenylalanine (F). 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
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
D;D;D
Sift4G
Benign
T;T;T
Polyphen
B;.;.
Vest4
MutPred
Gain of catalytic residue at L9 (P = 0.0016);Gain of catalytic residue at L9 (P = 0.0016);Gain of catalytic residue at L9 (P = 0.0016);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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