rs193920901

chr1-153763296-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_023015.5(INTS3):c.1700T>C(p.Ile567Thr) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: INTS3 NM_023015.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.49

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, INTS3
• BP4: Computational evidence support a benign effect (MetaRNN=0.2538213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS3	NM_023015.5	c.1700T>C	p.Ile567Thr	missense_variant	16/30	ENST00000318967.7
INTS3	NM_001324475.2	c.1700T>C	p.Ile567Thr	missense_variant	17/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS3	ENST00000318967.7	c.1700T>C	p.Ile567Thr	missense_variant	16/30	1	NM_023015.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
Cadd	Pathogenic	26
Dann	Uncertain	1.0
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.83	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0080	D;D;D
Sift4G	Benign	0.11	T;T;T
Polyphen		0.78	P;P;B
Vest4		0.59
MVP		0.20
MPC		1.5
ClinPred		0.96	D
GERP RS		5.1
gMVP		0.60

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: rs193920901; hg19: chr1-153735772; COSMIC: COSV59679787; COSMIC: COSV59679787;