12-91111527-A-AGGG

Variant names:

• chr12-91111527-A-AGGG
• rs3832846
• NM_002345.4:c.-152_-151insCCC

Variant summary

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

The NM_002345.4(LUM):​c.-152_-151insCCC variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.010 (49 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LUM NM_002345.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360
• Publications: 3 publications found

Genes affected

LUM (HGNC:6724): (lumican) This gene encodes a member of the small leucine-rich proteoglycan (SLRP) family that includes decorin, biglycan, fibromodulin, keratocan, epiphycan, and osteoglycin. In these bifunctional molecules, the protein moiety binds collagen fibrils and the highly charged hydrophilic glycosaminoglycans regulate interfibrillar spacings. Lumican is the major keratan sulfate proteoglycan of the cornea but is also distributed in interstitial collagenous matrices throughout the body. Lumican may regulate collagen fibril organization and circumferential growth, corneal transparency, and epithelial cell migration and tissue repair. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002345.4. 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
	LUM	NM_002345.4	MANE Select	c.-152_-151insCCC		upstream_gene	N/A	NP_002336.1	P51884

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUM	ENST00000266718.5	TSL:1 MANE Select	c.-152_-151insCCC		upstream_gene	N/A	ENSP00000266718.4	P51884
	LUM	ENST00000891369.1		c.-239_-238insCCC		upstream_gene	N/A	ENSP00000561428.1
	LUM	ENST00000963638.1		c.-147_-146insCCC		upstream_gene	N/A	ENSP00000633697.1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1555 AN: 148608 Hom.: 47 Cov.: 0

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00147

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000577

Gnomad OTH AF: 0.0142

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 36 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 26

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 32

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0105 AC: 1557 AN: 148714 Hom.: 49 Cov.: 0 AF XY: 0.0113 AC XY: 816 AN XY: 72518

African (AFR) AF: 0.0141 AC: 555 AN: 39470

American (AMR) AF: 0.0616 AC: 918 AN: 14908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5040

South Asian (SAS) AF: 0.00 AC: 0 AN: 4750

European-Finnish (FIN) AF: 0.00147 AC: 15 AN: 10228

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000577 AC: 39 AN: 67612

Other (OTH) AF: 0.0140 AC: 29 AN: 2068

Alfa AF: 0.00 Hom.: 1974

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36
Mutation Taster		=300/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3832846;

hg19: chr12-91505304;