chr5-90474001-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_203406.2(MBLAC2):​c.292G>T​(p.Val98Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,374 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V98M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MBLAC2
NM_203406.2 missense

Scores

3
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.22
Variant links:
Genes affected
MBLAC2 (HGNC:33711): (metallo-beta-lactamase domain containing 2) Enables palmitoyl-CoA hydrolase activity. Located in endoplasmic reticulum membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
POLR3G (HGNC:30075): (RNA polymerase III subunit G) Enables chromatin binding activity. Involved in positive regulation of innate immune response; positive regulation of interferon-beta production; and transcription by RNA polymerase III. Acts upstream of or within cell population proliferation. Located in cytosol and nuclear body. Part of RNA polymerase III complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MBLAC2NM_203406.2 linkc.292G>T p.Val98Leu missense_variant Exon 1 of 2 ENST00000316610.7 NP_981951.2 Q68D91-1B3KY36

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MBLAC2ENST00000316610.7 linkc.292G>T p.Val98Leu missense_variant Exon 1 of 2 1 NM_203406.2 ENSP00000314776.6 Q68D91-1
MBLAC2ENST00000514906.1 linkc.292G>T p.Val98Leu missense_variant Exon 1 of 1 6 ENSP00000425600.1 Q68D91-2
POLR3GENST00000512239.1 linkc.-44+2075C>A intron_variant Intron 1 of 1 5 ENSP00000424970.1 D6REQ0
POLR3GENST00000505345.5 linkc.-361C>A upstream_gene_variant 3 ENSP00000427412.1 D6RIT0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1446374
Hom.:
0
Cov.:
36
AF XY:
0.00000139
AC XY:
1
AN XY:
718162
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000511
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.68
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
T;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.79
T;T
M_CAP
Pathogenic
0.40
D
MetaRNN
Uncertain
0.74
D;D
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
0.19
N;N
REVEL
Uncertain
0.43
Sift
Benign
0.50
T;T
Sift4G
Benign
0.39
T;T
Polyphen
0.89
P;.
Vest4
0.64
MutPred
0.51
Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);
MVP
0.43
MPC
0.75
ClinPred
0.98
D
GERP RS
5.2
Varity_R
0.43
gMVP
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1179934133; hg19: chr5-89769818; API