chr7-1471160-G-A

Position:

• chr7-1471160-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080453.3(INTS1):​c.6320C>T​(p.Ala2107Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: INTS1 NM_001080453.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.49

Genes affected

INTS1 (HGNC:24555): (integrator complex subunit 1) INTS1 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INTS1	NM_001080453.3	c.6320C>T	p.Ala2107Val	missense_variant	46/48	ENST00000404767.8	NP_001073922.2
INTS1	XM_011515260.2	c.6350C>T	p.Ala2117Val	missense_variant	46/48		XP_011513562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS1	ENST00000404767.8	c.6320C>T	p.Ala2107Val	missense_variant	46/48	5	NM_001080453.3	ENSP00000385722	P1
INTS1	ENST00000483196.1	c.359C>T	p.Ala120Val	missense_variant	4/4	5		ENSP00000419206
INTS1	ENST00000493446.1	n.304C>T		non_coding_transcript_exon_variant	4/6	3
INTS1	ENST00000479671.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1427336 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 706742

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Mar 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T;.
Eigen	Benign	0.039
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.88	N;N
REVEL	Benign	0.23
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;.
Polyphen		0.076	B;.
Vest4		0.77
MutPred		0.56		Gain of catalytic residue at A2107 (P = 0.0312);.;
MVP		0.63
ClinPred		0.86	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.45

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: rs894183649; hg19: chr7-1510796;