9-38413334-C-T

Variant names:

• chr9-38413334-C-T
• rs140576184
• NM_001007563.3:c.590G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001007563.3(IGFBPL1):​c.590G>A​(p.Gly197Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G197V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IGFBPL1 NM_001007563.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.60
• Publications: 1 publications found

Genes affected

IGFBPL1 (HGNC:20081): (insulin like growth factor binding protein like 1) Predicted to enable insulin-like growth factor binding activity. Involved in cellular response to tumor cell. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.789

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007563.3. 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
	IGFBPL1	NM_001007563.3	MANE Select	c.590G>A	p.Gly197Asp	missense	Exon 3 of 5	NP_001007564.1	Q8WX77

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBPL1	ENST00000377694.2	TSL:2 MANE Select	c.590G>A	p.Gly197Asp	missense	Exon 3 of 5	ENSP00000366923.1	Q8WX77
	IGFBPL1	ENST00000906221.1		c.590G>A	p.Gly197Asp	missense	Exon 3 of 4	ENSP00000576280.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.75
MutPred		0.53		Gain of solvent accessibility (P = 0.0281)
MVP		0.89
MPC		1.0
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.84
gMVP		0.44
Mutation Taster		=70/30	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: rs140576184; hg19: chr9-38413331;