chr3-8548722-T-A

Variant names:

• chr3-8548722-T-A
• NM_014583.4:c.542T>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 17/22 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
• 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 0 ACMG points.

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

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.542T>A	p.Leu181Gln	missense	Exon 4 of 6	NP_055398.1	Q9NZU5-1
	LMCD1	NM_001278233.2		c.323T>A	p.Leu108Gln	missense	Exon 3 of 5	NP_001265162.1	Q9NZU5-2
	LMCD1	NM_001278234.2		c.206T>A	p.Leu69Gln	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.542T>A	p.Leu181Gln	missense	Exon 4 of 6	ENSP00000157600.3	Q9NZU5-1
	LMCD1	ENST00000880274.1		c.533T>A	p.Leu178Gln	missense	Exon 4 of 6	ENSP00000550333.1
	LMCD1	ENST00000957327.1		c.542T>A	p.Leu181Gln	missense	Exon 4 of 5	ENSP00000627386.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	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
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.68	N
PhyloP100		0.38
PrimateAI	Benign	0.37	T
PROVEAN	Benign	2.7	N
REVEL	Benign	0.21
Sift	Benign	0.41	T
Sift4G	Benign	0.56	T
Polyphen		0.48	P
Vest4		0.21
MutPred		0.61		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
Mutation Taster		=82/18	polymorphism

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: chr3-8590408;