NM_001306080.2:c.110C>A

Variant names:

• chr13-75713222-C-A
• rs1244575693
• NM_001306080.2:c.110C>A

Variant summary

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

The NM_001306080.2(LMO7):​c.110C>A​(p.Ala37Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,394 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A37V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LMO7 NM_001306080.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23
• Publications: 0 publications found

Genes affected

LMO7 (HGNC:6646): (LIM domain 7) This gene encodes a protein containing a calponin homology (CH) domain, a PDZ domain, and a LIM domain, and may be involved in protein-protein interactions. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene, however, the full-length nature of some variants is not known. [provided by RefSeq, Jan 2009]

ENSG00000261553 (HGNC:):

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, 0.803

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001306080.2. 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
	LMO7	NM_001306080.2	MANE Select	c.110C>A	p.Ala37Asp	missense	Exon 2 of 31	NP_001293009.1	F8WD26
	LMO7	NM_005358.5		c.266C>A	p.Ala89Asp	missense	Exon 3 of 30	NP_005349.3	Q8WWI1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO7	ENST00000377534.8	TSL:1 MANE Select	c.110C>A	p.Ala37Asp	missense	Exon 2 of 31	ENSP00000366757.4	F8WD26
	LMO7	ENST00000341547.8	TSL:1	c.266C>A	p.Ala89Asp	missense	Exon 3 of 30	ENSP00000342112.4	Q8WWI1-3
	LMO7	ENST00000357063.7	TSL:5	c.221C>A	p.Ala74Asp	missense	Exon 3 of 32	ENSP00000349571.4	J3KP06

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458394 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725642

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.00 AC: 0 AN: 85842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109910

Other (OTH) AF: 0.00 AC: 0 AN: 60226

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Benign	0.35	N
PhyloP100		4.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.69
Sift	Benign	0.22	T
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.84
MVP		0.95
ClinPred		0.98	D
GERP RS		5.6
gMVP		0.50
Mutation Taster		=78/22	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: rs1244575693; hg19: chr13-76287358;