rs1047991308

Variant names:

• chr11-65539092-C-A
• rs1047991308
• NM_001130144.3:c.3900G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-65539092-C-A
• chr11-65539092-C-G
• chr11-65539092-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001130144.3(LTBP3):​c.3900G>T​(p.Gln1300His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000235 in 1,276,418 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: LTBP3 NM_001130144.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28253514).

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.3900G>T	p.Gln1300His	missense	Exon 28 of 28	NP_001123616.1	Q9NS15-1
	LTBP3	NM_021070.4		c.3759G>T	p.Gln1253His	missense	Exon 27 of 27	NP_066548.2	Q9NS15-2
	LTBP3	NM_001164266.1		c.3408G>T	p.Gln1136His	missense	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.3900G>T	p.Gln1300His	missense	Exon 28 of 28	ENSP00000301873.5	Q9NS15-1
	LTBP3	ENST00000322147.8	TSL:1	c.3759G>T	p.Gln1253His	missense	Exon 27 of 27	ENSP00000326647.4	Q9NS15-2
	LTBP3	ENST00000528516.5	TSL:1	n.*3404G>T		non_coding_transcript_exon	Exon 27 of 27	ENSP00000432350.1	E9PRF2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 80458 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000235 AC: 3 AN: 1276418 Hom.: 0 Cov.: 31 AF XY: 0.00000320 AC XY: 2 AN XY: 625542

African (AFR) AF: 0.00 AC: 0 AN: 25274

American (AMR) AF: 0.00 AC: 0 AN: 22878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21464

East Asian (EAS) AF: 0.00 AC: 0 AN: 28392

South Asian (SAS) AF: 0.00 AC: 0 AN: 69794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3846

European-Non Finnish (NFE) AF: 0.00000294 AC: 3 AN: 1019478

Other (OTH) AF: 0.00 AC: 0 AN: 51880

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	0.85	L
PhyloP100		1.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.29
MutPred		0.37		Gain of catalytic residue at Q1300 (P = 0.0603)
MVP		0.79
ClinPred		0.88	D
GERP RS		4.9
Varity_R		0.29
gMVP		0.82
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

dbSNP: rs1047991308; hg19: chr11-65306563;