chr3-8548754-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014583.4(LMCD1):c.574G>A(p.Glu192Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
LMCD1
NM_014583.4 missense
NM_014583.4 missense
Scores
1
12
6
Clinical Significance
Conservation
PhyloP100: 6.91
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LMCD1 | NM_014583.4 | c.574G>A | p.Glu192Lys | missense_variant | 4/6 | ENST00000157600.8 | |
LMCD1 | NM_001278233.2 | c.355G>A | p.Glu119Lys | missense_variant | 3/5 | ||
LMCD1 | NM_001278234.2 | c.238G>A | p.Glu80Lys | missense_variant | 3/5 | ||
LMCD1 | NM_001278235.2 | c.574G>A | p.Glu192Lys | missense_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMCD1 | ENST00000157600.8 | c.574G>A | p.Glu192Lys | missense_variant | 4/6 | 1 | NM_014583.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152222Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251192Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135758
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461458Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726950
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74370
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 26, 2023 | The c.574G>A (p.E192K) alteration is located in exon 4 (coding exon 4) of the LMCD1 gene. This alteration results from a G to A substitution at nucleotide position 574, causing the glutamic acid (E) at amino acid position 192 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D;D
REVEL
Uncertain
Sift
Benign
D;.;D;T;T
Sift4G
Benign
T;D;T;D;T
Polyphen
P;.;P;.;.
Vest4
MutPred
Gain of ubiquitination at E192 (P = 0.0177);Gain of ubiquitination at E192 (P = 0.0177);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at