NM_001130144.3:c.3878_3907dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC

Variant names:

• chr11-65539084-C-CGGCGGCGCTGGGGAACGCAGGCCCCGTGCG
• NM_001130144.3:c.3878_3907dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001130144.3(LTBP3):​c.3878_3907dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC​(p.Pro1293_Arg1302dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R1303R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LTBP3 NM_001130144.3 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• Publications: 0 publications found

Genes affected

LTBP3 (HGNC:6716): (latent transforming growth factor beta binding protein 3) The protein encoded by this gene forms a complex with transforming growth factor beta (TGF-beta) proteins and may be involved in their subcellular localization. Activation of this complex requires removal of the encoded binding protein. This protein also may play a structural role in the extracellular matrix. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

LTBP3 Gene-Disease associations (from GenCC):

• brachyolmia-amelogenesis imperfecta syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• geleophysic dysplasia 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Acromicric dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• geleophysic dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001130144.3

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130144.3. 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
	LTBP3	NM_001130144.3	MANE Select	c.3878_3907dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC	p.Pro1293_Arg1302dup	conservative_inframe_insertion	Exon 28 of 28	NP_001123616.1	Q9NS15-1
	LTBP3	NM_021070.4		c.3737_3766dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC	p.Pro1246_Arg1255dup	conservative_inframe_insertion	Exon 27 of 27	NP_066548.2	Q9NS15-2
	LTBP3	NM_001164266.1		c.3386_3415dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC	p.Pro1129_Arg1138dup	conservative_inframe_insertion	Exon 27 of 27	NP_001157738.1	Q9NS15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP3	ENST00000301873.11	TSL:2 MANE Select	c.3878_3907dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC	p.Pro1293_Arg1302dup	conservative_inframe_insertion	Exon 28 of 28	ENSP00000301873.5	Q9NS15-1
	LTBP3	ENST00000322147.8	TSL:1	c.3737_3766dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC	p.Pro1246_Arg1255dup	conservative_inframe_insertion	Exon 27 of 27	ENSP00000326647.4	Q9NS15-2
	LTBP3	ENST00000528516.5	TSL:1	n.*3382_*3411dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC		non_coding_transcript_exon	Exon 27 of 27	ENSP00000432350.1	E9PRF2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Brachyolmia-amelogenesis imperfecta syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

Splicing

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

Other links and lift over

hg19: chr11-65306555;