Variant 19-17816972-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The NM_005543.4(INSL3):c.278C>T(p.Pro93Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000473 in 1,614,080 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00049 ( 1 hom. )

Consequence

INSL3
NM_005543.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.149

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP5

Variant 19-17816972-G-A is Pathogenic according to our data. Variant chr19-17816972-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 14830.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.32742023). . Strength limited to SUPPORTING due to the PP5.

BS2

High AC in GnomAd4 at 50 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSL3	NM_005543.4 linkuse as main transcript	c.278C>T	p.Pro93Leu	missense_variant	2/2	ENST00000317306.8	NP_005534.2
INSL3	NM_001265587.2 linkuse as main transcript	c.373C>T	p.Pro125Ser	missense_variant	3/3		NP_001252516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSL3	ENST00000317306.8 linkuse as main transcript	c.278C>T	p.Pro93Leu	missense_variant	2/2	1	NM_005543.4	ENSP00000321724	P1	P51460-1
INSL3	ENST00000379695.5 linkuse as main transcript	c.373C>T	p.Pro125Ser	missense_variant	3/3	1		ENSP00000369017		P51460-2
INSL3	ENST00000598577.1 linkuse as main transcript	c.*84C>T		3_prime_UTR_variant	2/2	1		ENSP00000469309

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000351

AC:

AN:

250912

Hom.:

AF XY:

0.000420

AC XY:

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000574

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000488

AC:

714

AN:

1461792

Hom.:

Cov.:

AF XY:

0.000477

AC XY:

347

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000575

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.000328

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000465

Hom.:

Bravo

AF:

0.000438

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000338

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000593

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Cryptorchidism

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.37

M_CAP

Benign

0.020

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.97

MutationTaster

Benign

8.9e-12

A;A

PROVEAN

Benign

-1.9

REVEL

Benign

0.18

Sift

Benign

0.27

Sift4G

Uncertain

0.028

Polyphen

0.010

Vest4

0.092

MVP

0.66

ClinPred

0.022

GERP RS

-0.71

Varity_R

0.035

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over