dbSNP rs143907741: LMCD1:p.Gly70Asp (chr3-8537262-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014583.4(LMCD1):c.209G>A(p.Gly70Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

LMCD1
NM_014583.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.48

Variant links:

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 links:

LMCD1-AS1 (HGNC:44477): (LMCD1 antisense RNA 1)

LMCD1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMCD1	NM_014583.4 link	c.209G>A	p.Gly70Asp	missense_variant	Exon 3 of 6	ENST00000157600.8	NP_055398.1	Q9NZU5-1
LMCD1	NM_001278235.2 link	c.209G>A	p.Gly70Asp	missense_variant	Exon 3 of 5		NP_001265164.1	Q9NZU5H7C3D2B7Z6R5
LMCD1	NM_001278233.2 link	c.-11G>A		5_prime_UTR_variant	Exon 2 of 5		NP_001265162.1	Q9NZU5-2
LMCD1	NM_001278234.2 link	c.51+4437G>A		intron_variant	Intron 2 of 4		NP_001265163.1	Q9NZU5B4DEY6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMCD1	ENST00000157600.8 link	c.209G>A	p.Gly70Asp	missense_variant	Exon 3 of 6	1	NM_014583.4	ENSP00000157600.3		Q9NZU5-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251200

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.39

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Pathogenic

0.34

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Uncertain

0.64

MutationAssessor

Uncertain

2.8

M;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.6

D;.;D

REVEL

Pathogenic

0.75

Sift

Uncertain

0.0070

D;.;T

Sift4G

Uncertain

0.014

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.97

MutPred

0.51

Loss of MoRF binding (P = 0.0627);Loss of MoRF binding (P = 0.0627);.;

MVP

0.98

MPC

1.2

ClinPred

0.92

GERP RS

4.6

Varity_R

0.34

gMVP

0.87

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over