chr5-159316699-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_002187.3(IL12B):c.973G>A(p.Val325Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,613,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002187.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL12B | NM_002187.3 | c.973G>A | p.Val325Met | missense_variant | 7/8 | ENST00000231228.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL12B | ENST00000231228.3 | c.973G>A | p.Val325Met | missense_variant | 7/8 | 1 | NM_002187.3 | P1 | |
IL12B | ENST00000696750.1 | c.343G>A | p.Val115Met | missense_variant | 4/5 | ||||
IL12B | ENST00000696751.1 | c.*468G>A | 3_prime_UTR_variant, NMD_transcript_variant | 6/7 | |||||
ENST00000521472.6 | n.289+5285C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000104 AC: 26AN: 248836Hom.: 0 AF XY: 0.0000892 AC XY: 12AN XY: 134480
GnomAD4 exome AF: 0.0000575 AC: 84AN: 1460898Hom.: 0 Cov.: 32 AF XY: 0.0000592 AC XY: 43AN XY: 726642
GnomAD4 genome AF: 0.0000656 AC: 10AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74488
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 02, 2023 | The c.973G>A (p.V325M) alteration is located in exon 7 (coding exon 6) of the IL12B gene. This alteration results from a G to A substitution at nucleotide position 973, causing the valine (V) at amino acid position 325 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 21, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 325 of the IL12B protein (p.Val325Met). This variant is present in population databases (rs56064925, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with IL12B-related conditions. ClinVar contains an entry for this variant (Variation ID: 541807). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at