1-116579656-C-CGTT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001007237.3(IGSF3):c.3069_3070insAAC(p.Asp1023_Asp1024insAsn) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,581,164 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (9 hom.)
• Consequence: IGSF3 NM_001007237.3 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00100

Genes affected

IGSF3 (HGNC:5950): (immunoglobulin superfamily member 3) The protein encoded by this gene is an immunoglobulin-like membrane protein containing several V-type Ig-like domains. A mutation in this gene has been associated with bilateral nasolacrimal duct obstruction (LCDD). [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-116579656-C-CGTT is Benign according to our data. Variant chr1-116579656-C-CGTT is described in ClinVar as [Benign]. Clinvar id is 3046067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF3	NM_001007237.3	c.3069_3070insAAC	p.Asp1023_Asp1024insAsn	inframe_insertion	10/11	ENST00000369486.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF3	ENST00000369486.8	c.3069_3070insAAC	p.Asp1023_Asp1024insAsn	inframe_insertion	10/11	1	NM_001007237.3	P4
IGSF3	ENST00000318837.6	c.3129_3130insAAC	p.Asp1043_Asp1044insAsn	inframe_insertion	10/11	2		A1
IGSF3	ENST00000369483.5	c.3129_3130insAAC	p.Asp1043_Asp1044insAsn	inframe_insertion	11/12	5		A1

Frequencies

GnomAD3 genomes AF: 0.00216 AC: 296 AN: 137332 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000200

Gnomad AMI AF: 0.00794

Gnomad AMR AF: 0.0000735

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.000526

GnomAD3 exomes AF: 0.00268 AC: 585 AN: 218442 Hom.: 6 AF XY: 0.00263 AC XY: 311 AN XY: 118122

Gnomad AFR exome AF: 0.0000660

Gnomad AMR exome AF: 0.0000625

Gnomad ASJ exome AF: 0.000110

Gnomad EAS exome AF: 0.000168

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0221

Gnomad NFE exome AF: 0.00196

Gnomad OTH exome AF: 0.00260

GnomAD4 exome AF: 0.00136 AC: 1961 AN: 1443696 Hom.: 9 Cov.: 59 AF XY: 0.00133 AC XY: 959 AN XY: 718760

Gnomad4 AFR exome AF: 0.0000307

Gnomad4 AMR exome AF: 0.0000453

Gnomad4 ASJ exome AF: 0.000118

Gnomad4 EAS exome AF: 0.000107

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0185

Gnomad4 NFE exome AF: 0.000839

Gnomad4 OTH exome AF: 0.00123

GnomAD4 genome AF: 0.00215 AC: 296 AN: 137468 Hom.: 3 Cov.: 32 AF XY: 0.00263 AC XY: 176 AN XY: 66872

Gnomad4 AFR AF: 0.000200

Gnomad4 AMR AF: 0.0000733

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0218

Gnomad4 NFE AF: 0.00150

Gnomad4 OTH AF: 0.000520

Alfa AF: 0.00118 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

IGSF3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs748093509; hg19: chr1-117122278;