GeneBe

12-65169598-TGGC-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting

The NM_014319.5(LEMD3):​c.9_11delGGC​(p.Ala4del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000000697 in 1,435,572 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

LEMD3
NM_014319.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.59
Variant links:
Genes affected
LEMD3 (HGNC:28887): (LEM domain containing 3) This locus encodes a LEM domain-containing protein. The encoded protein functions to antagonize transforming growth factor-beta signaling at the inner nuclear membrane. Two transcript variants encoding different isoforms have been found for this gene. Mutations in this gene have been associated with osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis.[provided by RefSeq, Nov 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_014319.5. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LEMD3NM_014319.5 linkc.9_11delGGC p.Ala4del disruptive_inframe_deletion Exon 1 of 13 ENST00000308330.3 NP_055134.2 Q9Y2U8A0A024RBB9
LEMD3NM_001167614.2 linkc.9_11delGGC p.Ala4del disruptive_inframe_deletion Exon 1 of 13 NP_001161086.1 Q9Y2U8
LOC124902953XR_007063349.1 linkn.-185_-183delGCC upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LEMD3ENST00000308330.3 linkc.9_11delGGC p.Ala4del disruptive_inframe_deletion Exon 1 of 13 1 NM_014319.5 ENSP00000308369.2 Q9Y2U8
LEMD3ENST00000541171.1 linkn.23_25delGGC non_coding_transcript_exon_variant Exon 1 of 2 2
ENSG00000289319ENST00000685904.1 linkn.-139_-137delGCC upstream_gene_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.97e-7
AC:
1
AN:
1435572
Hom.:
0
AF XY:
0.00000141
AC XY:
1
AN XY:
711742
show subpopulations
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:
9.08e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-65563378; API