chr3-127923861-T-C

Position:

• chr3-127923861-T-C

Variant summary

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

The NM_207335.4(KBTBD12):​c.800T>C​(p.Leu267Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KBTBD12 NM_207335.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.61

Genes affected

KBTBD12 (HGNC:25731): (kelch repeat and BTB domain containing 12)

KBTBD12 (HGNC:):

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]

ACMG classification

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
KBTBD12	NM_207335.4	c.800T>C	p.Leu267Pro	missense_variant	2/6	ENST00000405109.5	NP_997218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KBTBD12	ENST00000405109.5	c.800T>C	p.Leu267Pro	missense_variant	2/6	5	NM_207335.4	ENSP00000385957.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2024

The c.800T>C (p.L267P) alteration is located in exon 1 (coding exon 1) of the KBTBD12 gene. This alteration results from a T to C substitution at nucleotide position 800, causing the leucine (L) at amino acid position 267 to be replaced by a proline (P). 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	0.23
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	1.7	N;N
REVEL	Uncertain	0.46
Sift	Benign	0.12	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.87
MutPred		0.59		Loss of stability (P = 0.0081);Loss of stability (P = 0.0081);
MVP		0.65
MPC		0.37
ClinPred		0.79	D
GERP RS		5.5
Varity_R		0.26
gMVP		0.89

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: chr3-127642704;