rs1179153155

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017871.6(INTS11):c.1595G>A(p.Ser532Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,480,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

INTS11
NM_017871.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.96

Publications

0 publications found

Variant links:

Genes affected

INTS11 (HGNC:26052): (integrator complex subunit 11) The Integrator complex contains at least 12 subunits and associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates the 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690). INTS11, or CPSF3L, is the catalytic subunit of the Integrator complex (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

INTS11 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities
Inheritance: AR Classification: MODERATE Submitted by: G2P

INTS11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.09400985).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017871.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INTS11	NM_017871.6	MANE Select	c.1595G>A	p.Ser532Asn	missense	Exon 15 of 17	NP_060341.2
INTS11	NM_001256456.2		c.1613G>A	p.Ser538Asn	missense	Exon 17 of 19	NP_001243385.1	Q5TA45-5
INTS11	NM_001256460.2		c.1508G>A	p.Ser503Asn	missense	Exon 16 of 18	NP_001243389.1	Q5TA45-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INTS11	ENST00000435064.6	TSL:1 MANE Select	c.1595G>A	p.Ser532Asn	missense	Exon 15 of 17	ENSP00000413493.2	Q5TA45-1
INTS11	ENST00000323275.10	TSL:1	n.1983G>A		non_coding_transcript_exon	Exon 14 of 16
INTS11	ENST00000462432.5	TSL:1	n.2398G>A		non_coding_transcript_exon	Exon 11 of 13

Frequencies

GnomAD3 genomes

AF:

0.0000158

AC:

AN:

126488

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000394

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000202

AC:

AN:

148664

AF XY:

0.0000377

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000256

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000665

AC:

AN:

1353608

Hom.:

Cov.:

AF XY:

0.00000904

AC XY:

AN XY:

663950

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31944

American (AMR)

AF:

0.00

AC:

AN:

35240

Ashkenazi Jewish (ASJ)

AF:

0.0000409

AC:

AN:

24426

East Asian (EAS)

AF:

0.0000549

AC:

AN:

36442

South Asian (SAS)

AF:

0.00

AC:

AN:

78418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4080

European-Non Finnish (NFE)

AF:

0.00000480

AC:

AN:

1041508

Other (OTH)

AF:

0.0000178

AC:

AN:

56260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000158

AC:

AN:

126488

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

59860

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38174

American (AMR)

AF:

0.00

AC:

AN:

11572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2940

East Asian (EAS)

AF:

0.000394

AC:

AN:

5072

South Asian (SAS)

AF:

0.00

AC:

AN:

4294

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

144

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

56202

Other (OTH)

AF:

0.00

AC:

AN:

1652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0089

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.85

M_CAP

Benign

0.0065

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

PhyloP100

3.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.28

REVEL

Benign

0.086

Sift

Benign

0.48

Sift4G

Benign

0.58

Polyphen

0.0

Vest4

0.20

MutPred

0.32

Loss of ubiquitination at K535 (P = 0.07)

MVP

0.58

MPC

0.029

ClinPred

0.18

GERP RS

4.6

Varity_R

0.12

gMVP

0.20

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over