dbSNP rs12648: LMBRD1:p.Asp469Glu (chr6-69697573-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018368.4(LMBRD1):c.1407T>G(p.Asp469Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LMBRD1
NM_018368.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.44

Publications

34 publications found

Variant links:

Genes affected

LMBRD1 (HGNC:23038): (LMBR1 domain containing 1) This gene encodes a lysosomal membrane protein that may be involved in the transport and metabolism of cobalamin. This protein also interacts with the large form of the hepatitis delta antigen and may be required for the nucleocytoplasmic shuttling of the hepatitis delta virus. Mutations in this gene are associated with the vitamin B12 metabolism disorder termed, homocystinuria-megaloblastic anemia complementation type F.[provided by RefSeq, Oct 2009]

LMBRD1 Gene-Disease associations (from GenCC):

methylmalonic aciduria and homocystinuria type cblF
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen, Orphanet

LMBRD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22248644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMBRD1	NM_018368.4 link	c.1407T>G	p.Asp469Glu	missense_variant	Exon 14 of 16	ENST00000649934.3	NP_060838.3	Q9NUN5-1
LMBRD1	NM_001363722.2 link	c.1188T>G	p.Asp396Glu	missense_variant	Exon 14 of 16		NP_001350651.1
LMBRD1	NM_001367271.1 link	c.1188T>G	p.Asp396Glu	missense_variant	Exon 14 of 16		NP_001354200.1
LMBRD1	NM_001367272.1 link	c.1188T>G	p.Asp396Glu	missense_variant	Exon 14 of 16		NP_001354201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3 link	c.1407T>G	p.Asp469Glu	missense_variant	Exon 14 of 16		NM_018368.4	ENSP00000497690.1		Q9NUN5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1448966

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721722

African (AFR)

AF:

0.00

AC:

AN:

33282

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26026

East Asian (EAS)

AF:

0.00

AC:

AN:

39514

South Asian (SAS)

AF:

0.00

AC:

AN:

85940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52698

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101110

Other (OTH)

AF:

0.00

AC:

AN:

59972

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0079

T;T;.;.;.;.;.;.;.;.;.;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.68

.;T;.;.;.;.;T;.;.;.;.;.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.22

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.97

L;L;.;.;.;.;.;.;.;.;.;.;.

PhyloP100

3.4

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.050

N;.;.;N;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.12

Sift

Benign

0.33

T;.;.;T;.;.;.;.;.;.;.;.;.

Sift4G

Benign

0.37

T;.;.;T;.;.;.;.;.;.;.;.;.

Polyphen

0.013

B;B;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.068

MutPred

0.081

Gain of glycosylation at P471 (P = 0.1041);Gain of glycosylation at P471 (P = 0.1041);.;.;.;.;.;.;.;.;.;.;.;

MVP

0.13

MPC

0.093

ClinPred

0.30

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.42

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over