1-211941954-G-A

Variant summary

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

The NM_015434.4(INTS7):c.2759C>T(p.Thr920Ile) 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: 32)
• Consequence: INTS7 NM_015434.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.64

Genes affected

INTS7 (HGNC:24484): (integrator complex subunit 7) This gene encodes a subunit of the integrator complex. The integrator complex associates with the C-terminal domain of RNA polymerase II and mediates 3'-end processing of the small nuclear RNAs U1 and U2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

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	UniProt
INTS7	NM_015434.4	c.2759C>T	p.Thr920Ile	missense_variant	20/20	ENST00000366994.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS7	ENST00000366994.8	c.2759C>T	p.Thr920Ile	missense_variant	20/20	1	NM_015434.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.2759C>T (p.T920I) alteration is located in exon 20 (coding exon 20) of the INTS7 gene. This alteration results from a C to T substitution at nucleotide position 2759, causing the threonine (T) at amino acid position 920 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
Cadd	Pathogenic	27
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.075	T;.;.;.;.
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.63	D;D;D;D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	2.0	M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.1	D;D;D;D;.
REVEL	Uncertain	0.51
Sift	Uncertain	0.0060	D;D;D;D;.
Sift4G	Uncertain	0.031	D;D;D;D;D
Polyphen		1.0	D;D;D;.;.
Vest4		0.76
MutPred		0.40		Gain of sheet (P = 0.0477);.;.;.;.;
MVP		0.51
MPC		0.62
ClinPred		0.96	D
GERP RS		5.9
Varity_R		0.42
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-212115296;