Variant chr19-17821381-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005543.4(INSL3):c.126A>G(p.Leu42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,548,232 control chromosomes in the GnomAD database, including 104,071 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10499 hom., cov: 35)

Exomes 𝑓: 0.36 ( 93572 hom. )

Consequence

INSL3
NM_005543.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0300

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 19-17821381-T-C is Benign according to our data. Variant chr19-17821381-T-C is described in ClinVar as [Benign]. Clinvar id is 1271020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-17821381-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSL3	NM_005543.4 linkuse as main transcript	c.126A>G	p.Leu42=	synonymous_variant	1/2	ENST00000317306.8	NP_005534.2
INSL3	NM_001265587.2 linkuse as main transcript	c.126A>G	p.Leu42=	synonymous_variant	1/3		NP_001252516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSL3	ENST00000317306.8 linkuse as main transcript	c.126A>G	p.Leu42=	synonymous_variant	1/2	1	NM_005543.4	ENSP00000321724	P1	P51460-1
INSL3	ENST00000379695.5 linkuse as main transcript	c.126A>G	p.Leu42=	synonymous_variant	1/3	1		ENSP00000369017		P51460-2
INSL3	ENST00000598577.1 linkuse as main transcript	c.126A>G	p.Leu42=	synonymous_variant	1/2	1		ENSP00000469309

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

55094

AN:

152070

Hom.:

10491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.422

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.362

GnomAD3 exomes

AF:

0.305

AC:

43412

AN:

142460

Hom.:

7645

AF XY:

0.299

AC XY:

22902

AN XY:

76700

show subpopulations

Gnomad AFR exome

AF:

0.383

Gnomad AMR exome

AF:

0.288

Gnomad ASJ exome

AF:

0.317

Gnomad EAS exome

AF:

0.00867

Gnomad SAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.428

Gnomad NFE exome

AF:

0.380

Gnomad OTH exome

AF:

0.339

GnomAD4 exome

AF:

0.357

AC:

498736

AN:

1396044

Hom.:

93572

Cov.:

AF XY:

0.352

AC XY:

242607

AN XY:

688458

show subpopulations

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.294

Gnomad4 ASJ exome

AF:

0.319

Gnomad4 EAS exome

AF:

0.00566

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.431

Gnomad4 NFE exome

AF:

0.382

Gnomad4 OTH exome

AF:

0.336

GnomAD4 genome

AF:

0.362

AC:

55137

AN:

152188

Hom.:

10499

Cov.:

AF XY:

0.358

AC XY:

26641

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.393

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.318

Gnomad4 EAS

AF:

0.0110

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.422

Gnomad4 NFE

AF:

0.387

Gnomad4 OTH

AF:

0.358

Alfa

AF:

0.380

Hom.:

3861

Bravo

AF:

0.355

Asia WGS

AF:

0.0970

AC:

339

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Cryptorchidism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.3

DANN

Benign

0.68

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