13-75621782-T-C

Variant names:

• chr13-75621782-T-C
• rs2033327427
• ENST00000341547.8:c.89T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005358.5(LMO7):​c.89T>C​(p.Leu30Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/16 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LMO7 NM_005358.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.509

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:):

LMO7-AS1 (HGNC:50277): (LMO7 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19171861).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMO7	NM_005358.5	c.89T>C	p.Leu30Pro	missense_variant	Exon 1 of 30		NP_005349.3
LMO7	XM_047430323.1	c.-767T>C		5_prime_UTR_variant	Exon 1 of 34		XP_047286279.1
LMO7	XM_047430329.1	c.-767T>C		5_prime_UTR_variant	Exon 1 of 33		XP_047286285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMO7	ENST00000341547.8	c.89T>C	p.Leu30Pro	missense_variant	Exon 1 of 30	1		ENSP00000342112.4
LMO7	ENST00000357063.7	c.44T>C	p.Leu15Pro	missense_variant	Exon 1 of 32	5		ENSP00000349571.4
ENSG00000261553	ENST00000563635.5	n.618T>C		non_coding_transcript_exon_variant	Exon 8 of 15	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461286 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726968

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.89T>C (p.L30P) alteration is located in exon 1 (coding exon 1) of the LMO7 gene. This alteration results from a T to C substitution at nucleotide position 89, causing the leucine (L) at amino acid position 30 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.031	T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	.;N
PROVEAN	Benign	-0.81	.;N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.049	.;B
Vest4		0.60
MVP		0.45
ClinPred		0.26	T
GERP RS		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2033327427; hg19: chr13-76195918;