chr8-19817548-A-G

Position:

• chr8-19817548-A-G

Variant summary

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

The NM_018142.4(INTS10):​c.11A>G​(p.Gln4Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: INTS10 NM_018142.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.05

Genes affected

INTS10 (HGNC:25548): (integrator complex subunit 10) INTS10 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

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=0.13314047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS10	NM_018142.4	c.11A>G	p.Gln4Arg	missense_variant	1/17	ENST00000397977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS10	ENST00000397977.8	c.11A>G	p.Gln4Arg	missense_variant	1/17	2	NM_018142.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455756 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723702

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Feb 07, 2023

The c.11A>G (p.Q4R) alteration is located in exon 1 (coding exon 1) of the INTS10 gene. This alteration results from a A to G substitution at nucleotide position 11, causing the glutamine (Q) at amino acid position 4 to be replaced by an arginine (R). 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
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	0.0085	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.098
Eigen_PC	Benign	0.089
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.99	D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.12
Sift	Benign	0.30	T
Sift4G	Benign	0.70	T
Polyphen		0.036	B
Vest4		0.36
MutPred		0.13		Gain of methylation at Q4 (P = 0.1239);
MVP		0.22
MPC		0.36
ClinPred		0.51	D
GERP RS		3.9
Varity_R		0.30
gMVP		0.61

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: rs1263310532; hg19: chr8-19675059;