rs10878252

Positions:

• chr12-65242286-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000308330.3(LEMD3):​c.2306-1102C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 152,146 control chromosomes in the GnomAD database, including 86 homozygotes. 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: 𝑓 0.015 (86 hom., cov: 32)
• Consequence: LEMD3 ENST00000308330.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEMD3	NM_014319.5	c.2306-1102C>G		intron_variant		ENST00000308330.3	NP_055134.2
LEMD3	NM_001167614.2	c.2303-1102C>G		intron_variant			NP_001161086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEMD3	ENST00000308330.3	c.2306-1102C>G		intron_variant		1	NM_014319.5	ENSP00000308369	P1
LEMD3	ENST00000542032.1	n.523-1102C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2326 AN: 152028 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0201

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.0115

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0153 AC: 2331 AN: 152146 Hom.: 86 Cov.: 32 AF XY: 0.0179 AC XY: 1332 AN XY: 74364

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.0200

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.00137

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00842 Hom.: 4

Bravo AF: 0.0155

Asia WGS AF: 0.0790 AC: 273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.5
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10878252; hg19: chr12-65636066;