chr3-8548694-C-A

Variant names:

• chr3-8548694-C-A
• rs566518812
• NM_014583.4:c.514C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014583.4(LMCD1):​c.514C>A​(p.Arg172Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R172P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LMCD1 NM_014583.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.514C>A	p.Arg172Ser	missense	Exon 4 of 6	NP_055398.1	Q9NZU5-1
	LMCD1	NM_001278233.2		c.295C>A	p.Arg99Ser	missense	Exon 3 of 5	NP_001265162.1	Q9NZU5-2
	LMCD1	NM_001278234.2		c.178C>A	p.Arg60Ser	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.514C>A	p.Arg172Ser	missense	Exon 4 of 6	ENSP00000157600.3	Q9NZU5-1
	LMCD1	ENST00000880274.1		c.505C>A	p.Arg169Ser	missense	Exon 4 of 6	ENSP00000550333.1
	LMCD1	ENST00000957327.1		c.514C>A	p.Arg172Ser	missense	Exon 4 of 5	ENSP00000627386.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.050	N
REVEL	Uncertain	0.47
Sift	Benign	0.13	T
Sift4G	Benign	0.098	T
Polyphen		0.91	P
Vest4		0.44
MutPred		0.61		Gain of phosphorylation at R172 (P = 0.0537)
MVP		0.90
MPC		0.63
ClinPred		0.73	D
GERP RS		5.8
Varity_R		0.21
gMVP		0.23
Mutation Taster		=57/43	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

dbSNP: rs566518812; hg19: chr3-8590380;