chr19-17816591-C-T

Position:

• chr19-17816591-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005543.4(INSL3):​c.*263G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 548,378 control chromosomes in the GnomAD database, including 119,954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35554 hom., cov: 32)
  • Exomes 𝑓: 0.65 (84400 hom.)
• Consequence: INSL3 NM_005543.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.233

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 19-17816591-C-T is Benign according to our data. Variant chr19-17816591-C-T is described in ClinVar as [Benign]. Clinvar id is 1174416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSL3	NM_005543.4	c.*263G>A		3_prime_UTR_variant	2/2	ENST00000317306.8	NP_005534.2
INSL3	NM_001265587.2	c.*280G>A		3_prime_UTR_variant	3/3		NP_001252516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSL3	ENST00000317306.8	c.*263G>A		3_prime_UTR_variant	2/2	1	NM_005543.4	ENSP00000321724	P1
INSL3	ENST00000379695.5	c.*280G>A		3_prime_UTR_variant	3/3	1		ENSP00000369017
INSL3	ENST00000598577.1	c.*465G>A		3_prime_UTR_variant	2/2	1		ENSP00000469309

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103529 AN: 151894 Hom.: 35500 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.651

GnomAD4 exome AF: 0.650 AC: 257581 AN: 396366 Hom.: 84400 Cov.: 2 AF XY: 0.646 AC XY: 134842 AN XY: 208590

Gnomad4 AFR exome AF: 0.749

Gnomad4 AMR exome AF: 0.627

Gnomad4 ASJ exome AF: 0.604

Gnomad4 EAS exome AF: 0.652

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.731

Gnomad4 NFE exome AF: 0.647

Gnomad4 OTH exome AF: 0.653

GnomAD4 genome AF: 0.682 AC: 103630 AN: 152012 Hom.: 35554 Cov.: 32 AF XY: 0.684 AC XY: 50816 AN XY: 74304

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.647

Alfa AF: 0.649 Hom.: 40453

Bravo AF: 0.677

Asia WGS AF: 0.606 AC: 2107 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.45

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

Other links and lift over

dbSNP: rs1003887; hg19: chr19-17927400;