1-211944878-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015434.4(INTS7):c.2507A>G(p.Gln836Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 7.63

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS7	NM_015434.4	c.2507A>G	p.Gln836Arg	missense_variant	19/20	ENST00000366994.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS7	ENST00000366994.8	c.2507A>G	p.Gln836Arg	missense_variant	19/20	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

Jun 24, 2022

The c.2507A>G (p.Q836R) alteration is located in exon 19 (coding exon 19) of the INTS7 gene. This alteration results from a A to G substitution at nucleotide position 2507, causing the glutamine (Q) at amino acid position 836 to be replaced by an arginine (R). 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	Uncertain	0.51
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.070	T;.;.;.
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.8	L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Benign	0.29
Sift	Benign	0.22	T;T;T;T
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.98	D;D;P;.
Vest4		0.90
MutPred		0.51		Gain of MoRF binding (P = 0.0135);.;.;.;
MVP		0.48
MPC		0.44
ClinPred		0.87	D
GERP RS		5.6
Varity_R		0.31
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-212118220;