chr3-8537303-C-G

Position:

• chr3-8537303-C-G

Variant summary

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

The NM_014583.4(LMCD1):​c.250C>G​(p.Arg84Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LMCD1 NM_014583.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46

Genes affected

LMCD1 (HGNC:6633): (LIM and cysteine rich domains 1) This gene encodes a member of the LIM-domain family of zinc finger proteins. The encoded protein contains an N-terminal cysteine-rich domain and two C-terminal LIM domains. The presence of LIM domains suggests involvement in protein-protein interactions. The protein may act as a co-regulator of transcription along with other transcription factors. Alternate splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

LMCD1-AS1 (HGNC:44477): (LMCD1 antisense RNA 1)

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
LMCD1	NM_014583.4	c.250C>G	p.Arg84Gly	missense_variant	3/6	ENST00000157600.8	NP_055398.1
LMCD1	NM_001278233.2	c.31C>G	p.Arg11Gly	missense_variant	2/5		NP_001265162.1
LMCD1	NM_001278235.2	c.250C>G	p.Arg84Gly	missense_variant	3/5		NP_001265164.1
LMCD1	NM_001278234.2	c.51+4478C>G		intron_variant			NP_001265163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMCD1	ENST00000157600.8	c.250C>G	p.Arg84Gly	missense_variant	3/6	1	NM_014583.4	ENSP00000157600.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000193 Hom.: 0

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

Sep 08, 2024

The c.250C>G (p.R84G) alteration is located in exon 3 (coding exon 3) of the LMCD1 gene. This alteration results from a C to G substitution at nucleotide position 250, causing the arginine (R) at amino acid position 84 to be replaced by a glycine (G). 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	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T;T;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Uncertain	-0.051	T
MutationAssessor	Uncertain	2.6	M;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.3	N;.;D;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0050	D;.;D;D
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.70	P;.;.;.
Vest4		0.73
MutPred		0.44		Loss of stability (P = 0.0111);Loss of stability (P = 0.0111);.;.;
MVP		0.89
MPC		1.1
ClinPred		0.96	D
GERP RS		3.8
Varity_R		0.26
gMVP		0.82

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

Other links and lift over

dbSNP: rs761332410; hg19: chr3-8578989;