1-153772652-G-C

Position:

• chr1-153772652-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_023015.5(INTS3):​c.2835G>C​(p.Thr945=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 1,613,996 control chromosomes in the GnomAD database, including 9,293 homozygotes. 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: 𝑓 0.15 (3278 hom., cov: 32)
  • Exomes 𝑓: 0.071 (6015 hom.)
• Consequence: INTS3 NM_023015.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=-0.795 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INTS3	NM_023015.5	c.2835G>C	p.Thr945=	synonymous_variant	28/30	ENST00000318967.7	NP_075391.3
INTS3	NM_001324475.2	c.2835G>C	p.Thr945=	synonymous_variant	29/31		NP_001311404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS3	ENST00000318967.7	c.2835G>C	p.Thr945=	synonymous_variant	28/30	1	NM_023015.5	ENSP00000318641	P1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 23020 AN: 152038 Hom.: 3258 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0855

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.00674

Gnomad SAS AF: 0.0826

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.135

GnomAD3 exomes AF: 0.0845 AC: 21229 AN: 251370 Hom.: 1882 AF XY: 0.0809 AC XY: 10989 AN XY: 135876

Gnomad AFR exome AF: 0.390

Gnomad AMR exome AF: 0.0563

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.00527

Gnomad SAS exome AF: 0.0838

Gnomad FIN exome AF: 0.0410

Gnomad NFE exome AF: 0.0661

Gnomad OTH exome AF: 0.0859

GnomAD4 exome AF: 0.0710 AC: 103765 AN: 1461840 Hom.: 6015 Cov.: 32 AF XY: 0.0709 AC XY: 51541 AN XY: 727210

Gnomad4 AFR exome AF: 0.397

Gnomad4 AMR exome AF: 0.0587

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.00418

Gnomad4 SAS exome AF: 0.0871

Gnomad4 FIN exome AF: 0.0396

Gnomad4 NFE exome AF: 0.0612

Gnomad4 OTH exome AF: 0.0891

GnomAD4 genome AF: 0.152 AC: 23089 AN: 152156 Hom.: 3278 Cov.: 32 AF XY: 0.149 AC XY: 11095 AN XY: 74404

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.0852

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.00676

Gnomad4 SAS AF: 0.0819

Gnomad4 FIN AF: 0.0431

Gnomad4 NFE AF: 0.0634

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0615 Hom.: 163

Bravo AF: 0.164

Asia WGS AF: 0.0650 AC: 226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.3
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs6663011; hg19: chr1-153745128; COSMIC: COSV55162666; COSMIC: COSV55162666;