3-8548722-T-A

Position:

• chr3-8548722-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014583.4(LMCD1):​c.542T>A​(p.Leu181Gln) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LMCD1 NM_014583.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.376

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.095507205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMCD1	NM_014583.4	c.542T>A	p.Leu181Gln	missense_variant	4/6	ENST00000157600.8	NP_055398.1
LMCD1	NM_001278233.2	c.323T>A	p.Leu108Gln	missense_variant	3/5		NP_001265162.1
LMCD1	NM_001278234.2	c.206T>A	p.Leu69Gln	missense_variant	3/5		NP_001265163.1
LMCD1	NM_001278235.2	c.542T>A	p.Leu181Gln	missense_variant	4/5		NP_001265164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMCD1	ENST00000157600.8	c.542T>A	p.Leu181Gln	missense_variant	4/6	1	NM_014583.4	ENSP00000157600.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Jan 23, 2023

The c.542T>A (p.L181Q) alteration is located in exon 4 (coding exon 4) of the LMCD1 gene. This alteration results from a T to A substitution at nucleotide position 542, causing the leucine (L) at amino acid position 181 to be replaced by a glutamine (Q). 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	0.071
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Benign	0.90
DEOGEN2	Benign	0.012	T;T;T;T;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.84	T;T;T;T;T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.096	T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.68	N;.;.;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	2.7	N;.;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.41	T;.;T;T;T
Sift4G	Benign	0.56	T;T;T;T;T
Polyphen		0.48	P;.;B;.;.
Vest4		0.21
MutPred		0.61		Gain of disorder (P = 0.0188);Gain of disorder (P = 0.0188);.;.;.;
MVP		0.72
MPC		0.81
ClinPred		0.15	T
GERP RS		3.0
Varity_R		0.071
gMVP		0.16

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: chr3-8590408;