9-5233869-T-G

Variant names:

• chr9-5233869-T-G
• NM_002195.2:c.412T>G

Variant summary

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

The NM_002195.2(INSL4):​c.412T>G​(p.Cys138Gly) 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: INSL4 NM_002195.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.187
• Publications: 0 publications found

Genes affected

INSL4 (HGNC:6087): (insulin like 4) INSL4 encodes the insulin-like 4 protein, a member of the insulin superfamily. INSL4 encodes a precursor that undergoes post-translational cleavage to produce 3 polypeptide chains, A-C, that form tertiary structures composed of either all three chains, or just the A and B chains. Expression of INSL4 products occurs within the early placental cytotrophoblast and syncytiotrophoblast. [provided by RefSeq, Jul 2008]

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_002195.2. 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
	INSL4	NM_002195.2	MANE Select	c.412T>G	p.Cys138Gly	missense	Exon 2 of 2	NP_002186.1	Q14641

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INSL4	ENST00000239316.4	TSL:1 MANE Select	c.412T>G	p.Cys138Gly	missense	Exon 2 of 2	ENSP00000239316.4	Q14641

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

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	0.71
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	13
DANN	Benign	0.64
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Benign	0.0	N
PhyloP100		0.19
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-8.2	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.51
MutPred		0.55		Gain of relative solvent accessibility (P = 0.0027)
MVP		0.85
MPC		0.0049
ClinPred		0.64	D
GERP RS		1.5
Varity_R		0.73
gMVP		0.22
Mutation Taster		=84/16	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

hg19: chr9-5233869;