21-33722544-G-GT

Position:

• chr21-33722544-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_003024.3(ITSN1):​c.122-29dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 118,780 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (13 hom., cov: 31)
  • Exomes 𝑓: 0.27 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: ITSN1 NM_003024.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.274

Genes affected

ITSN1 (HGNC:6183): (intersectin 1) The protein encoded by this gene is a cytoplasmic membrane-associated protein that indirectly coordinates endocytic membrane traffic with the actin assembly machinery. In addition, the encoded protein may regulate the formation of clathrin-coated vesicles and could be involved in synaptic vesicle recycling. This protein has been shown to interact with dynamin, CDC42, SNAP23, SNAP25, SPIN90, EPS15, EPN1, EPN2, and STN2. Multiple transcript variants encoding different isoforms have been found for this gene, but the full-length nature of only two of them have been characterized so far. [provided by RefSeq, Jul 2008]

ENSG00000249209 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 21-33722544-G-GT is Benign according to our data. Variant chr21-33722544-G-GT is described in ClinVar as [Benign]. Clinvar id is 1280299.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0138 (1643/118780) while in subpopulation SAS AF= 0.0203 (73/3588). AF 95% confidence interval is 0.018. There are 13 homozygotes in gnomad4. There are 832 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1643 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITSN1	NM_003024.3	c.122-29dupT		intron_variant		ENST00000381318.8	NP_003015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITSN1	ENST00000381318.8	c.122-29dupT		intron_variant		1	NM_003024.3	ENSP00000370719.3
ENSG00000249209	ENST00000429238.2	c.442-136364dupA		intron_variant		5		ENSP00000394107.2

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 1643 AN: 118768 Hom.: 13 Cov.: 31

Gnomad AFR AF: 0.00498

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.00719

Gnomad ASJ AF: 0.00799

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0307

Gnomad MID AF: 0.0172

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.0117

GnomAD3 exomes AF: 0.163 AC: 13953 AN: 85614 Hom.: 0 AF XY: 0.169 AC XY: 8195 AN XY: 48350

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.0903

Gnomad SAS exome AF: 0.215

Gnomad FIN exome AF: 0.220

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.179

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.265 AC: 258743 AN: 975434 Hom.: 3 Cov.: 0 AF XY: 0.261 AC XY: 126702 AN XY: 485694

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.0138 AC: 1643 AN: 118780 Hom.: 13 Cov.: 31 AF XY: 0.0144 AC XY: 832 AN XY: 57596

Gnomad4 AFR AF: 0.00497

Gnomad4 AMR AF: 0.00718

Gnomad4 ASJ AF: 0.00799

Gnomad4 EAS AF: 0.00368

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.0307

Gnomad4 NFE AF: 0.0190

Gnomad4 OTH AF: 0.0110

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

May 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs373376953; hg19: chr21-35094849;