3-8565586-C-T

Variant summary

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

The NM_014583.4(LMCD1):c.878C>T(p.Ala293Val) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LMCD1 NM_014583.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3224417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMCD1	NM_014583.4	c.878C>T	p.Ala293Val	missense_variant	5/6	ENST00000157600.8
LMCD1	NM_001278233.2	c.659C>T	p.Ala220Val	missense_variant	4/5
LMCD1	NM_001278234.2	c.542C>T	p.Ala181Val	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMCD1	ENST00000157600.8	c.878C>T	p.Ala293Val	missense_variant	5/6	1	NM_014583.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Feb 28, 2023

The c.878C>T (p.A293V) alteration is located in exon 5 (coding exon 5) of the LMCD1 gene. This alteration results from a C to T substitution at nucleotide position 878, causing the alanine (A) at amino acid position 293 to be replaced by a valine (V). 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	0.076
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;.
Eigen	Benign	-0.052
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.89	D;D;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Uncertain	-0.065	T
MutationAssessor	Benign	0.46	N;.;.
MutationTaster	Benign	0.82	D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.086	T;D;D
Sift4G	Benign	0.21	T;T;T
Polyphen		0.018	B;B;.
Vest4		0.40
MutPred		0.49		Gain of methylation at K290 (P = 0.0984);.;.;
MVP		0.83
MPC		0.33
ClinPred		0.64	D
GERP RS		5.7
Varity_R		0.098
gMVP		0.58

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: rs1000714171; hg19: chr3-8607272;