12-26925858-GA-G

Variant summary

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

The NM_018164.3(INTS13):c.585-8del variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.00221 in 1,607,188 control chromosomes in the GnomAD database, including 62 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (36 hom.)
• Consequence: INTS13 NM_018164.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.42

Genes affected

INTS13 (HGNC:20174): (integrator complex subunit 13) Involved in regulation of mitotic cell cycle. Acts upstream of or within centrosome localization; mitotic spindle organization; and protein localization to nuclear envelope. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-26925858-GA-G is Benign according to our data. Variant chr12-26925858-GA-G is described in ClinVar as [Benign]. Clinvar id is 781068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1739/152248) while in subpopulation AFR AF= 0.0391 (1626/41554). AF 95% confidence interval is 0.0375. There are 26 homozygotes in gnomad4. There are 798 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS13	NM_018164.3	c.585-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000261191.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS13	ENST00000261191.12	c.585-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018164.3	P1
INTS13	ENST00000538727.5	c.282-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		4
INTS13	ENST00000544548.5	c.585-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1730 AN: 152130 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00861

GnomAD3 exomes AF: 0.00296 AC: 737 AN: 249026 Hom.: 14 AF XY: 0.00230 AC XY: 310 AN XY: 134580

Gnomad AFR exome AF: 0.0400

Gnomad AMR exome AF: 0.00195

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000333

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00125 AC: 1817 AN: 1454940 Hom.: 36 Cov.: 27 AF XY: 0.00108 AC XY: 780 AN XY: 724036

Gnomad4 AFR exome AF: 0.0419

Gnomad4 AMR exome AF: 0.00203

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000701

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000130

Gnomad4 OTH exome AF: 0.00281

GnomAD4 genome AF: 0.0114 AC: 1739 AN: 152248 Hom.: 26 Cov.: 32 AF XY: 0.0107 AC XY: 798 AN XY: 74444

Gnomad4 AFR AF: 0.0391

Gnomad4 AMR AF: 0.00543

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.00109 Hom.: 2

Bravo AF: 0.0131

Asia WGS AF: 0.00116 AC: 4 AN: 3466

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

Invitae

May 14, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs201480298; hg19: chr12-27078791;