19-46123973-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207393.2(IGFL3):​c.263G>A​(p.Gly88Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IGFL3
NM_207393.2 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54
Variant links:
Genes affected
IGFL3 (HGNC:32930): (IGF like family member 3) IGFL3 belongs to the insulin-like growth factor (IGF; see MIM 147440) family of signaling molecules that play critical roles in cellular energy metabolism and in growth and development, especially prenatal growth (Emtage et al., 2006 [PubMed 16890402]).[supplied by OMIM, Mar 2008]
IGFL2 (HGNC:32929): (IGF like family member 2) IGFL2 belongs to the insulin-like growth factor (IGF; see MIM 147440) family of signaling molecules that play critical roles in cellular energy metabolism and in growth and development, especially prenatal growth (Emtage et al., 2006 [PubMed 16890402]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.18192157).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IGFL3NM_207393.2 linkc.263G>A p.Gly88Asp missense_variant Exon 3 of 4 ENST00000341415.3 NP_997276.1 Q6UXB1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IGFL3ENST00000341415.3 linkc.263G>A p.Gly88Asp missense_variant Exon 3 of 4 1 NM_207393.2 ENSP00000344860.2 Q6UXB1
ENSG00000267922ENST00000597989.1 linkn.16+22836C>T intron_variant Intron 1 of 3 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460578
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726602
show subpopulations
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.263G>A (p.G88D) alteration is located in exon 3 (coding exon 3) of the IGFL3 gene. This alteration results from a G to A substitution at nucleotide position 263, causing the glycine (G) at amino acid position 88 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.036
T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.40
T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.0
M
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.030
Sift
Benign
0.053
T
Sift4G
Uncertain
0.020
D
Polyphen
0.99
D
Vest4
0.20
MutPred
0.29
Loss of catalytic residue at G88 (P = 0.0319);
MVP
0.14
MPC
1.0
ClinPred
0.67
D
GERP RS
1.6
Varity_R
0.21
gMVP
0.25

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1008228073; hg19: chr19-46627230; API