rs193920901

Variant names:

• chr1-153763296-T-C
• rs193920901
• NM_023015.5:c.1700T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2538213).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023015.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS3	NM_023015.5	MANE Select	c.1700T>C	p.Ile567Thr	missense	Exon 16 of 30	NP_075391.3
	INTS3	NM_001324475.2		c.1700T>C	p.Ile567Thr	missense	Exon 17 of 31	NP_001311404.1	Q68E01-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS3	ENST00000318967.7	TSL:1 MANE Select	c.1700T>C	p.Ile567Thr	missense	Exon 16 of 30	ENSP00000318641.2	Q68E01-2
	INTS3	ENST00000476843.5	TSL:1	n.*323T>C		non_coding_transcript_exon	Exon 11 of 25	ENSP00000485263.1	A0A096LNW8
	INTS3	ENST00000476843.5	TSL:1	n.*323T>C		3_prime_UTR	Exon 11 of 25	ENSP00000485263.1	A0A096LNW8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
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
MetaSVM	Benign	-0.83	T
PhyloP100		7.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.25
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.11	T
Polyphen		0.78	P
Vest4		0.59
MVP		0.20
MPC		1.5
ClinPred		0.96	D
GERP RS		5.1
gMVP		0.60
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

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