12-65169620-G-A

Variant names:

• chr12-65169620-G-A
• rs1380930067
• NM_014319.5:c.24G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_014319.5(LEMD3):​c.24G>A​(p.Ala8Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,436,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: LEMD3 NM_014319.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95

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]

ENSG00000289319 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BS2: High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LEMD3	NM_014319.5	c.24G>A	p.Ala8Ala	synonymous_variant	Exon 1 of 13	ENST00000308330.3	NP_055134.2
LEMD3	NM_001167614.2	c.24G>A	p.Ala8Ala	synonymous_variant	Exon 1 of 13		NP_001161086.1
LOC124902953	XR_007063349.1	n.-204C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LEMD3	ENST00000308330.3	c.24G>A	p.Ala8Ala	synonymous_variant	Exon 1 of 13	1	NM_014319.5	ENSP00000308369.2
LEMD3	ENST00000541171.1	n.38G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
ENSG00000289319	ENST00000685904.1	n.-158C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000125 AC: 18 AN: 1436320 Hom.: 0 Cov.: 32 AF XY: 0.0000112 AC XY: 8 AN XY: 712286

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000136

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.94

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

LitVar

Other links and lift over

dbSNP: rs1380930067; hg19: chr12-65563400;