11-65539092-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3	c.3900G>T	p.Gln1300His	missense_variant	Exon 28 of 28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.3759G>T	p.Gln1253His	missense_variant	Exon 27 of 27		NP_066548.2
LTBP3	NM_001164266.1	c.3408G>T	p.Gln1136His	missense_variant	Exon 27 of 27		NP_001157738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11	c.3900G>T	p.Gln1300His	missense_variant	Exon 28 of 28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes Cov.: 33

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000294

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	0.85	.;L;.;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.2	N;N;N;N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.014	D;D;T;T;T
Sift4G	Uncertain	0.011	D;D;T;D;T
Polyphen		0.99	D;D;.;.;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

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: rs1047991308; hg19: chr11-65306563;