rs193920933

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

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>T​(p.Gly365Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LMLN NM_001136049.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 8.50
• Publications: 1 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, 0.982

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136049.3. 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
	LMLN	NM_001136049.3	MANE Select	c.1093G>T	p.Gly365Cys	missense	Exon 10 of 17	NP_001129521.3	Q96KR4-3
	LMLN	NM_033029.4		c.1093G>T	p.Gly365Cys	missense	Exon 10 of 16	NP_149018.3	Q96KR4-1
	LMLN	NR_026786.2		n.1001G>T		non_coding_transcript_exon	Exon 10 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMLN	ENST00000420910.7	TSL:1 MANE Select	c.1093G>T	p.Gly365Cys	missense	Exon 10 of 17	ENSP00000410926.3	Q96KR4-3
	LMLN	ENST00000330198.8	TSL:1	c.1093G>T	p.Gly365Cys	missense	Exon 10 of 16	ENSP00000328829.5	Q96KR4-1
	LMLN	ENST00000482695.5	TSL:1	c.397G>T	p.Gly133Cys	missense	Exon 10 of 17	ENSP00000418324.2	A0AAA9XCN5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452588 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 722698

⚠️ 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: 32794

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

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

East Asian (EAS) AF: 0.0000257 AC: 1 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: 0.00 AC: 0 AN: 1107794

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

⚠️ 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.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.80	D
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.66	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		8.5
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-8.2	D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.90		Loss of disorder (P = 0.0179)
MVP		0.86
MPC		1.3
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.84
gMVP		0.95
Mutation Taster		=15/85	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; COSMIC: COSV57603857; COSMIC: COSV57603857;