3-127923531-A-G

Variant summary

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

The NM_207335.4(KBTBD12):ā€‹c.470A>Gā€‹(p.Tyr157Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,054 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

KBTBD12
NM_207335.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.86
Variant links:
Genes affected
KBTBD12 (HGNC:25731): (kelch repeat and BTB domain containing 12)
MGLL (HGNC:17038): (monoglyceride lipase) This gene encodes a serine hydrolase of the AB hydrolase superfamily that catalyzes the conversion of monoacylglycerides to free fatty acids and glycerol. The encoded protein plays a critical role in several physiological processes including pain and nociperception through hydrolysis of the endocannabinoid 2-arachidonoylglycerol. Expression of this gene may play a role in cancer tumorigenesis and metastasis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

Genome browser will be placed here

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/exons MANE Protein UniProt
KBTBD12NM_207335.4 linkuse as main transcriptc.470A>G p.Tyr157Cys missense_variant 2/6 ENST00000405109.5 NP_997218.2 Q3ZCT8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KBTBD12ENST00000405109.5 linkuse as main transcriptc.470A>G p.Tyr157Cys missense_variant 2/65 NM_207335.4 ENSP00000385957.1 Q3ZCT8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460054
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
726196
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsJan 03, 2024The c.470A>G (p.Y157C) alteration is located in exon 1 (coding exon 1) of the KBTBD12 gene. This alteration results from a A to G substitution at nucleotide position 470, causing the tyrosine (Y) at amino acid position 157 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.012
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
16
DANN
Benign
0.94
DEOGEN2
Benign
0.19
T;T
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.19
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.84
.;T
M_CAP
Benign
0.040
D
MetaRNN
Uncertain
0.51
D;D
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
0.90
L;L
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.23
Sift
Benign
0.19
T;T
Sift4G
Benign
0.18
T;T
Polyphen
0.035
B;B
Vest4
0.61
MutPred
0.57
Gain of methylation at K154 (P = 0.0497);Gain of methylation at K154 (P = 0.0497);
MVP
0.43
MPC
0.052
ClinPred
0.22
T
GERP RS
4.6
Varity_R
0.11
gMVP
0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-127642374; API