3-8548572-T-C

Variant names:

• chr3-8548572-T-C
• NM_014583.4:c.392T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014583.4(LMCD1):​c.392T>C​(p.Leu131Pro) 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 pathogenic 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: 3.31
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.768

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014583.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMCD1	NM_014583.4	MANE Select	c.392T>C	p.Leu131Pro	missense	Exon 4 of 6	NP_055398.1	Q9NZU5-1
	LMCD1	NM_001278233.2		c.173T>C	p.Leu58Pro	missense	Exon 3 of 5	NP_001265162.1	Q9NZU5-2
	LMCD1	NM_001278234.2		c.56T>C	p.Leu19Pro	missense	Exon 3 of 5	NP_001265163.1	B4DEY6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMCD1	ENST00000157600.8	TSL:1 MANE Select	c.392T>C	p.Leu131Pro	missense	Exon 4 of 6	ENSP00000157600.3	Q9NZU5-1
	LMCD1	ENST00000957327.1		c.392T>C	p.Leu131Pro	missense	Exon 4 of 5	ENSP00000627386.1
	LMCD1	ENST00000454244.4	TSL:2	c.173T>C	p.Leu58Pro	missense	Exon 3 of 5	ENSP00000396515.1	Q9NZU5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.048	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	-0.072	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.3
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N
REVEL	Pathogenic	0.65
Sift	Benign	0.19	T
Sift4G	Benign	0.30	T
Polyphen		0.77	P
Vest4		0.63
MutPred		0.68		Gain of disorder (P = 0.0203)
MVP		0.96
MPC		1.1
ClinPred		0.87	D
GERP RS		5.3
Varity_R		0.63
gMVP		0.66
Mutation Taster		=34/66	disease causing

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

Other links and lift over

hg19: chr3-8590258;