1-1312237-GC-CG

Variant names:

• chr1-1312237-GC-CG
• NM_017871.6:c.1595_1596delGCinsCG
• INTS11 p.Ser532Thr

Variant summary

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

The NM_017871.6(INTS11):​c.1595_1596delGCinsCG​(p.Ser532Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S532N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: INTS11 NM_017871.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• 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 0 ACMG points.

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.1595_1596delGCinsCG	p.Ser532Thr	missense	N/A	NP_060341.2
	INTS11	NM_001256456.2		c.1613_1614delGCinsCG	p.Ser538Thr	missense	N/A	NP_001243385.1	Q5TA45-5
	INTS11	NM_001256460.2		c.1508_1509delGCinsCG	p.Ser503Thr	missense	N/A	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.1595_1596delGCinsCG	p.Ser532Thr	missense	N/A	ENSP00000413493.2	Q5TA45-1
	INTS11	ENST00000323275.10	TSL:1	n.1983_1984delGCinsCG		non_coding_transcript_exon	Exon 14 of 16
	INTS11	ENST00000462432.5	TSL:1	n.2398_2399delGCinsCG		non_coding_transcript_exon	Exon 11 of 13

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

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: chr1-1247617;