19-46123892-C-T

Variant names:

• chr19-46123892-C-T
• rs1213749878
• NM_207393.2:c.344G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207393.2(IGFL3):​c.344G>A​(p.Cys115Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGFL3 NM_207393.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64
• Publications: 0 publications found

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]

ENSG00000267922 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207393.2. 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
	IGFL3	NM_207393.2	MANE Select	c.344G>A	p.Cys115Tyr	missense	Exon 3 of 4	NP_997276.1	Q6UXB1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFL3	ENST00000341415.3	TSL:1 MANE Select	c.344G>A	p.Cys115Tyr	missense	Exon 3 of 4	ENSP00000344860.2	Q6UXB1
	ENSG00000267922	ENST00000597989.1	TSL:5	n.16+22755C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0026	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-8.1	D
REVEL	Benign	0.095
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.57		Gain of MoRF binding (P = 0.0781)
MVP		0.095
MPC		1.2
ClinPred		0.97	D
GERP RS		1.4
Varity_R		0.74
gMVP		0.60
Mutation Taster		=94/6	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: rs1213749878; hg19: chr19-46627149;