chr12-65169605-G-C

Variant names:

• chr12-65169605-G-C
• rs763192267
• NM_014319.5:c.9G>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_014319.5(LEMD3):​c.9G>C​(p.Ala3Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LEMD3 NM_014319.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.854

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 12-65169605-G-C is Benign according to our data. Variant chr12-65169605-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3632673.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.854 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LEMD3	NM_014319.5	c.9G>C	p.Ala3Ala	synonymous_variant	Exon 1 of 13	ENST00000308330.3	NP_055134.2
LEMD3	NM_001167614.2	c.9G>C	p.Ala3Ala	synonymous_variant	Exon 1 of 13		NP_001161086.1
LOC124902953	XR_007063349.1	n.-189C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LEMD3	ENST00000308330.3	c.9G>C	p.Ala3Ala	synonymous_variant	Exon 1 of 13	1	NM_014319.5	ENSP00000308369.2
LEMD3	ENST00000541171.1	n.23G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
ENSG00000289319	ENST00000685904.1	n.-143C>G		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	13
DANN	Benign	0.84

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: rs763192267; hg19: chr12-65563385;