11-65546547-C-G

Variant names:

• chr11-65546547-C-G
• NM_001130144.3:c.2248G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001130144.3(LTBP3):​c.2248G>C​(p.Glu750Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LTBP3 NM_001130144.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24184585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3	c.2248G>C	p.Glu750Gln	missense_variant	Exon 16 of 28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.2248G>C	p.Glu750Gln	missense_variant	Exon 16 of 27		NP_066548.2
LTBP3	NM_001164266.1	c.1897G>C	p.Glu633Gln	missense_variant	Exon 16 of 27		NP_001157738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11	c.2248G>C	p.Glu750Gln	missense_variant	Exon 16 of 28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449948 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721762

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;T;.;T;T
Eigen	Benign	-0.071
Eigen_PC	Benign	-0.017
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.87	D;T;T;T;D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.3	L;L;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.5	N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.31	T;T;T;T;T
Sift4G	Benign	0.14	T;T;T;.;T
Polyphen		1.0	D;D;D;D;.
Vest4		0.48
MutPred		0.36		Loss of glycosylation at S752 (P = 0.1123);Loss of glycosylation at S752 (P = 0.1123);.;.;.;
MVP		0.87
ClinPred		0.81	D
GERP RS		5.0
Varity_R		0.22
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65314018;