INTS11 p.Pro547Pro

Variant names:

• chr1-1312113-C-C
• NM_017871.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-1312114--
• chr1-1312114-T-A
• chr1-1312114-T-G
• chr1-1312114-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017871.6(INTS11):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 25)
• Consequence: INTS11 NM_017871.6 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• Publications: 0 publications found

Genes affected

INTS11 (HGNC:26052): (integrator complex subunit 11) The Integrator complex contains at least 12 subunits and associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates the 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690). INTS11, or CPSF3L, is the catalytic subunit of the Integrator complex (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

INTS11 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities

  Inheritance: AR Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017871.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS11	NM_017871.6	MANE Select	c.		exon_region	Exon 16 of 17	NP_060341.2
	INTS11	NM_001256456.2		c.		exon_region	Exon 18 of 19	NP_001243385.1	Q5TA45-5
	INTS11	NM_001256460.2		c.		exon_region	Exon 17 of 18	NP_001243389.1	Q5TA45-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS11	ENST00000435064.6	TSL:1 MANE Select	c.		exon_region	Exon 16 of 17	ENSP00000413493.2	Q5TA45-1
	INTS11	ENST00000323275.10	TSL:1	n.		exon_region	Exon 15 of 16
	INTS11	ENST00000462432.5	TSL:1	n.		exon_region	Exon 12 of 13

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-1247493;