Variant 8-19833185-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018142.4(INTS10):c.1394C>T(p.Ala465Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,602,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

INTS10
NM_018142.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.50

Variant links:

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]

INTS10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.911

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS10	NM_018142.4 linkuse as main transcript	c.1394C>T	p.Ala465Val	missense_variant	12/17	ENST00000397977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
INTS10	ENST00000397977.8 linkuse as main transcript	c.1394C>T	p.Ala465Val	missense_variant	12/17	2	NM_018142.4	P1
INTS10	ENST00000518799.1 linkuse as main transcript	c.143C>T	p.Ala48Val	missense_variant	3/5	5
INTS10	ENST00000519493.1 linkuse as main transcript	n.27C>T		non_coding_transcript_exon_variant	2/3	5
INTS10	ENST00000521357.5 linkuse as main transcript	c.*240C>T		3_prime_UTR_variant, NMD_transcript_variant	4/7	5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000210

AC:

AN:

238458

Hom.:

AF XY:

0.0000231

AC XY:

AN XY:

129764

show subpopulations

Gnomad AFR exome

AF:

0.0000665

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000241

AC:

AN:

1450720

Hom.:

Cov.:

AF XY:

0.0000263

AC XY:

AN XY:

721786

show subpopulations

Gnomad4 AFR exome

AF:

0.0000612

Gnomad4 AMR exome

AF:

0.0000238

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000289

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000819

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.0000552

EpiControl

AF:

0.000120

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

The c.1394C>T (p.A465V) alteration is located in exon 12 (coding exon 12) of the INTS10 gene. This alteration results from a C to T substitution at nucleotide position 1394, causing the alanine (A) at amino acid position 465 to be replaced by a valine (V). 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

Pathogenic

0.75

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.0058

MetaRNN

Pathogenic

0.91

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.2

REVEL

Benign

0.18

Sift

Benign

0.37

Sift4G

Uncertain

0.013

Polyphen

0.99

Vest4

0.87

MutPred

0.80

Gain of methylation at K464 (P = 0.041);

MVP

0.23

MPC

0.93

ClinPred

0.80

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over