rs193920933

Variant names:

• chr3-197996244-G-A
• rs193920933
• NM_001136049.3:c.1093G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-197996244-G-A
• chr3-197996244-G-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001136049.3(LMLN):​c.1093G>A​(p.Gly365Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,452,588 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. G365C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: LMLN NM_001136049.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.50
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMLN	NM_001136049.3	c.1093G>A	p.Gly365Ser	missense_variant	Exon 10 of 17	ENST00000420910.7	NP_001129521.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMLN	ENST00000420910.7	c.1093G>A	p.Gly365Ser	missense_variant	Exon 10 of 17	1	NM_001136049.3	ENSP00000410926.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000413 AC: 6 AN: 1452588 Hom.: 0 Cov.: 28 AF XY: 0.00000553 AC XY: 4 AN XY: 722698

African (AFR) AF: 0.00 AC: 0 AN: 32794

American (AMR) AF: 0.00 AC: 0 AN: 43178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25956

East Asian (EAS) AF: 0.00 AC: 0 AN: 38856

South Asian (SAS) AF: 0.00 AC: 0 AN: 85030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000542 AC: 6 AN: 1107794

Other (OTH) AF: 0.00 AC: 0 AN: 59968

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	.;D;.;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.98	D;D;D;D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Uncertain	2.5	.;M;M;.
PhyloP100		8.5
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.5	D;D;D;D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.93
MutPred		0.93		.;Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;
MVP		0.83
MPC		1.2
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.67
gMVP		0.88
Mutation Taster		=17/83	disease causing

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: rs193920933; hg19: chr3-197723115;