1-87332215-A-G

Position:

• chr1-87332215-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006769.4(LMO4):​c.200A>G​(p.Lys67Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LMO4 NM_006769.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.26

Genes affected

LMO4 (HGNC:6644): (LIM domain only 4) This gene encodes a cysteine-rich protein that contains two LIM domains but lacks a DNA-binding homeodomain. The encoded protein may play a role as a transcriptional regulator or as an oncogene. [provided by RefSeq, Aug 2008]

LMO4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29881188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMO4	NM_006769.4	c.200A>G	p.Lys67Arg	missense_variant	2/5	ENST00000370544.10	NP_006760.1
LMO4	NM_001369491.1	c.200A>G	p.Lys67Arg	missense_variant	2/5		NP_001356420.1
LMO4	XM_047432941.1	c.200A>G	p.Lys67Arg	missense_variant	3/6		XP_047288897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMO4	ENST00000370544.10	c.200A>G	p.Lys67Arg	missense_variant	2/5	1	NM_006769.4	ENSP00000359575.4
LMO4	ENST00000370542.1	c.200A>G	p.Lys67Arg	missense_variant	2/5	1		ENSP00000359573.1
LMO4	ENST00000489303.1	n.435A>G		non_coding_transcript_exon_variant	1/4	2
LMO4	ENST00000495705.5	n.432A>G		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Oct 04, 2022

The c.200A>G (p.K67R) alteration is located in exon 2 (coding exon 1) of the LMO4 gene. This alteration results from a A to G substitution at nucleotide position 200, causing the lysine (K) at amino acid position 67 to be replaced by an arginine (R). 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	0.12
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T;T
Eigen	Benign	-0.039
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.33	N;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.41
Sift	Benign	0.23	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.28	B;B
Vest4		0.30
MutPred		0.72		Loss of ubiquitination at K67 (P = 0.0183);Loss of ubiquitination at K67 (P = 0.0183);
MVP		0.78
MPC		1.1
ClinPred		0.82	D
GERP RS		5.8
Varity_R		0.33
gMVP		0.55

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: chr1-87797898;