19-17817058-AC-GT

Variant names:

• chr19-17817058-AC-GT
• ENST00000598577.1:c.210_211delGTinsAC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The ENST00000598577.1(INSL3):​c.210_211delGTinsAC​(p.Ter71Argext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: INSL3 ENST00000598577.1 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 0 publications found

Genes affected

INSL3 (HGNC:6086): (insulin like 3) This gene encodes a member of the insulin-like hormone superfamily. The encoded protein is mainly produced in gonadal tissues. Studies of the mouse counterpart suggest that this gene may be involved in the development of urogenital tract and female fertility. This protein may also act as a hormone to regulate growth and differentiation of gubernaculum, and thus mediating intra-abdominal testicular descent. Mutations in this gene may lead to cryptorchidism. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

INSL3 Gene-Disease associations (from GenCC):

• cryptorchidism

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

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

• PM4: Stoplost variant in ENST00000598577.1 Downstream stopcodon found after 41 codons.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000598577.1. 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
	INSL3	NM_005543.4	MANE Select	c.191_192delGTinsAC	p.Arg64His	missense splice_region	N/A	NP_005534.2
	INSL3	NM_001265587.2		c.286_287delGTinsAC	p.Val96Thr	missense splice_region	N/A	NP_001252516.1	P51460-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INSL3	ENST00000598577.1	TSL:1	c.210_211delGTinsAC	p.Ter71Argext*?	stop_lost	N/A	ENSP00000469309.1	M0QXQ3
	INSL3	ENST00000317306.8	TSL:1 MANE Select	c.191_192delGTinsAC	p.Arg64His	missense splice_region	N/A	ENSP00000321724.6	P51460-1
	INSL3	ENST00000379695.5	TSL:1	c.286_287delGTinsAC	p.Val96Thr	missense splice_region	N/A	ENSP00000369017.4	P51460-2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-17927867;