11-77878961-AGG-TGC

Variant names:

• chr11-77878961-AGG-TGC
• NM_033547.4:c.2878_2880delCCTinsGCA
• INTS4 p.Pro960Ala

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_033547.4(INTS4):​c.2878_2880delCCTinsGCA​(p.Pro960Ala) variant causes a missense change involving the alteration of a 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P960T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INTS4 NM_033547.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.21
• Publications: 0 publications found

Genes affected

INTS4 (HGNC:25048): (integrator complex subunit 4) INTS4 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

AAMDC (HGNC:30205): (adipogenesis associated Mth938 domain containing) Predicted to be involved in positive regulation of fat cell differentiation. Predicted to act upstream of or within negative regulation of apoptotic process and positive regulation of transcription by RNA polymerase II. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033547.4. 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
	INTS4	NM_033547.4	MANE Select	c.2878_2880delCCTinsGCA	p.Pro960Ala	missense	N/A	NP_291025.3
	AAMDC	NM_001316957.3		c.328+1912_328+1914delAGGinsTGC		intron	N/A	NP_001303886.1	K4DI89
	AAMDC	NM_001316958.3		c.383+205_383+207delAGGinsTGC		intron	N/A	NP_001303887.1	E9PLK9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS4	ENST00000534064.6	TSL:1 MANE Select	c.2878_2880delCCTinsGCA	p.Pro960Ala	missense	N/A	ENSP00000434466.1	Q96HW7-1
	AAMDC	ENST00000304716.12	TSL:1	c.328+1912_328+1914delAGGinsTGC		intron	N/A	ENSP00000307254.8	K4DI89
	AAMDC	ENST00000532481.5	TSL:1	c.228+9144_228+9146delAGGinsTGC		intron	N/A	ENSP00000433293.1	Q9H7C9-3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.2

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: chr11-77590007;