11-65539392-C-G

Variant names:

• chr11-65539392-C-G
• NM_001130144.3:c.3696G>C
• LTBP3 p.Pro1232Pro

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001130144.3(LTBP3):​c.3696G>C​(p.Pro1232Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P1232P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LTBP3 NM_001130144.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.32
• 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
• geleophysic dysplasia 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.005).
• BP7: Synonymous conserved (PhyloP=-4.32 with no splicing effect.

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.3696G>C	p.Pro1232Pro	synonymous	Exon 27 of 28	NP_001123616.1	Q9NS15-1
	LTBP3	NM_021070.4		c.3555G>C	p.Pro1185Pro	synonymous	Exon 26 of 27	NP_066548.2	Q9NS15-2
	LTBP3	NM_001164266.1		c.3204G>C	p.Pro1068Pro	synonymous	Exon 26 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.3696G>C	p.Pro1232Pro	synonymous	Exon 27 of 28	ENSP00000301873.5	Q9NS15-1
	LTBP3	ENST00000322147.8	TSL:1	c.3555G>C	p.Pro1185Pro	synonymous	Exon 26 of 27	ENSP00000326647.4	Q9NS15-2
	LTBP3	ENST00000528516.5	TSL:1	n.*3200G>C		non_coding_transcript_exon	Exon 26 of 27	ENSP00000432350.1	E9PRF2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.14
DANN	Benign	0.69
PhyloP100		-4.3

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-65306863;