NM_023015.5:c.318+408G>C

Variant names:

• chr1-153741776-G-C
• rs12041194
• NM_023015.5:c.318+408G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_023015.5(INTS3):​c.318+408G>C variant causes a intron 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. 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS3	NM_023015.5	c.318+408G>C		intron_variant	Intron 3 of 29	ENST00000318967.7	NP_075391.3
INTS3	NM_001324475.2	c.318+408G>C		intron_variant	Intron 4 of 30		NP_001311404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS3	ENST00000318967.7	c.318+408G>C		intron_variant	Intron 3 of 29	1	NM_023015.5	ENSP00000318641.2
INTS3	ENST00000435409.6	c.318+408G>C		intron_variant	Intron 4 of 30	2		ENSP00000404290.2
INTS3	ENST00000481797.5	n.470+408G>C		intron_variant	Intron 3 of 28	2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.5
DANN	Benign	0.54

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: rs12041194; hg19: chr1-153714252;