Variant 19-17816920-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_001265587.2(INSL3):c.425C>T(p.Thr142Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

INSL3
NM_001265587.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.80

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 -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11008397).

BS2

High AC in GnomAdExome4 at 7 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.330C>T	p.Asn110Asn	synonymous_variant	2/2	ENST00000317306.8	NP_005534.2	P51460-1
INSL3	NM_001265587.2 linkuse as main transcript	c.425C>T	p.Thr142Ile	missense_variant	3/3		NP_001252516.1	P51460-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
INSL3	ENST00000379695.5 linkuse as main transcript	c.425C>T	p.Thr142Ile	missense_variant	3/3	1		ENSP00000369017.4	P51460-2
INSL3	ENST00000317306.8 linkuse as main transcript	c.330C>T	p.Asn110Asn	synonymous_variant	2/2	1	NM_005543.4	ENSP00000321724.6	P51460-1
INSL3	ENST00000598577 linkuse as main transcript	c.*136C>T		3_prime_UTR_variant	2/2	1		ENSP00000469309.1	M0QXQ3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251316

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000625

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.0

DANN

Uncertain

0.99

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.36

M_CAP

Benign

0.046

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.71

REVEL

Benign

0.065

Sift

Benign

0.38

Sift4G

Benign

0.26

Vest4

0.14

MutPred

0.25

Loss of glycosylation at T142 (P = 0.0025);

MVP

0.29

MPC

0.27

ClinPred

0.92

GERP RS

2.8

gMVP

0.033

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over