19-17817089-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000598577.1(INSL3):c.190-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,598,660 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (64 hom., cov: 31)
  • Exomes 𝑓: 0.0014 (53 hom.)
• Consequence: INSL3 ENST00000598577.1 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003076
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0580

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-17817089-G-A is Benign according to our data. Variant chr19-17817089-G-A is described in ClinVar as [Benign]. Clinvar id is 1249049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INSL3	NM_005543.4	c.191-30C>T		intron_variant		ENST00000317306.8
INSL3	NM_001265587.2	c.286-30C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INSL3	ENST00000317306.8	c.191-30C>T		intron_variant		1	NM_005543.4	P1
INSL3	ENST00000379695.5	c.286-30C>T		intron_variant		1
INSL3	ENST00000598577.1	c.190-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2101 AN: 152142 Hom.: 63 Cov.: 31

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00370 AC: 842 AN: 227574 Hom.: 22 AF XY: 0.00248 AC XY: 307 AN XY: 123802

Gnomad AFR exome AF: 0.0522

Gnomad AMR exome AF: 0.00172

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000138

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000196

Gnomad OTH exome AF: 0.00210

GnomAD4 exome AF: 0.00143 AC: 2070 AN: 1446400 Hom.: 53 Cov.: 29 AF XY: 0.00116 AC XY: 837 AN XY: 719446

Gnomad4 AFR exome AF: 0.0525

Gnomad4 AMR exome AF: 0.00231

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000153

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000127

Gnomad4 OTH exome AF: 0.00303

GnomAD4 genome AF: 0.0139 AC: 2120 AN: 152260 Hom.: 64 Cov.: 31 AF XY: 0.0133 AC XY: 989 AN XY: 74448

Gnomad4 AFR AF: 0.0494

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.0125 Hom.: 22

Bravo AF: 0.0160

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	7.8
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000031
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -8

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

Publications

LitVar

Other links and lift over

dbSNP: rs74531687; hg19: chr19-17927898;