1-153771892-T-A

Position:

• chr1-153771892-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023015.5(INTS3):​c.2649T>A​(p.His883Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INTS3 NM_023015.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.882

Genes affected

INTS3 (HGNC:26153): (integrator complex subunit 3) The protein encoded by this gene can form a complex with human single-strand DNA binding proteins 1 or 2 (hSSB1 and hSSB2) and other proteins to mediate genome stability and the DNA damage response. The encoded protein is also part of a multiprotein complex that interacts with the C-terminal domain of RNA polymerase II large subunit to help regulate processing of U1 and U2 small nuclear RNAs. [provided by RefSeq, May 2016]

INTS3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13090745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INTS3	NM_023015.5	c.2649T>A	p.His883Gln	missense_variant	26/30	ENST00000318967.7	NP_075391.3
INTS3	NM_001324475.2	c.2649T>A	p.His883Gln	missense_variant	27/31		NP_001311404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS3	ENST00000318967.7	c.2649T>A	p.His883Gln	missense_variant	26/30	1	NM_023015.5	ENSP00000318641.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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 05, 2024

The c.2649T>A (p.H883Q) alteration is located in exon 26 (coding exon 26) of the INTS3 gene. This alteration results from a T to A substitution at nucleotide position 2649, causing the histidine (H) at amino acid position 883 to be replaced by a glutamine (Q). 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
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	3.7
DANN	Benign	0.97
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.45	N
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Benign	0.14
Sift	Benign	0.030	D;D;D
Sift4G	Uncertain	0.017	D;D;T
Polyphen		0.72	P;P;P
Vest4		0.30
MVP		0.29
MPC		1.3
ClinPred		0.74	D
GERP RS		-4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.47

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: chr1-153744368;