3-197976705-A-G

Position:

• chr3-197976705-A-G

Variant summary

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

The NM_001136049.3(LMLN):​c.515A>G​(p.Glu172Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LMLN NM_001136049.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.03

Genes affected

LMLN (HGNC:15991): (leishmanolysin like peptidase) This gene encodes a zinc-metallopeptidase. The encoded protein may play a role in cell migration and invasion. Studies of a similar protein in Drosophila indicate a potential role in mitotic progression. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

ACMG classification

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	Protein	UniProt
LMLN	NM_001136049.3	c.515A>G	p.Glu172Gly	missense_variant	5/17	ENST00000420910.7	NP_001129521.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMLN	ENST00000420910.7	c.515A>G	p.Glu172Gly	missense_variant	5/17	1	NM_001136049.3	ENSP00000410926

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1372574 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 679260

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2023

The c.539A>G (p.E180G) alteration is located in exon 5 (coding exon 5) of the LMLN gene. This alteration results from a A to G substitution at nucleotide position 539, causing the glutamic acid (E) at amino acid position 180 to be replaced by a glycine (G). 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
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	.;D;.;.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.56	D;D;D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.3	.;M;.;M;.
MutationTaster	Benign	0.91	D;D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.0	D;D;D;D;D
REVEL	Benign	0.23
Sift	Benign	0.031	D;D;D;D;D
Sift4G	Benign	0.071	T;T;D;T;T
Polyphen		0.84	P;P;.;.;P
Vest4		0.38
MutPred		0.52		.;Loss of stability (P = 0.0434);.;Loss of stability (P = 0.0434);.;
MVP		0.65
MPC		0.87
ClinPred		0.99	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.23
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs1207771341; hg19: chr3-197703576;