Variant chr12-26917727-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018164.3(INTS13):c.896C>T(p.Ser299Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000592 in 1,604,214 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S299T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 1 hom. )

Consequence

INTS13
NM_018164.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

Variant links:

Genes affected

INTS13 (HGNC:20174): (integrator complex subunit 13) Involved in regulation of mitotic cell cycle. Acts upstream of or within centrosome localization; mitotic spindle organization; and protein localization to nuclear envelope. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

INTS13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 (MetaRNN=0.01834938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS13	NM_018164.3 linkuse as main transcript	c.896C>T	p.Ser299Leu	missense_variant	9/17	ENST00000261191.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS13	ENST00000261191.12 linkuse as main transcript	c.896C>T	p.Ser299Leu	missense_variant	9/17	1	NM_018164.3	P1	Q9NVM9-1
INTS13	ENST00000538155.5 linkuse as main transcript	c.8C>T	p.Ser3Leu	missense_variant	1/8	5
INTS13	ENST00000536232.1 linkuse as main transcript	c.163-286C>T		intron_variant		3
INTS13	ENST00000542392.4 linkuse as main transcript	n.36C>T		non_coding_transcript_exon_variant	2/6	5

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

151808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

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:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.0000518

AC:

AN:

251180

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.0000324

AC:

AN:

1452406

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

722628

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000540

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000813

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000452

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

AF:

0.000316

AC:

AN:

151808

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

74118

show subpopulations

Gnomad4 AFR

AF:

0.0000726

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.000763

ExAC

AF:

0.0000165

AC:

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

Sep 12, 2023

The c.896C>T (p.S299L) alteration is located in exon 9 (coding exon 8) of the ASUN gene. This alteration results from a C to T substitution at nucleotide position 896, causing the serine (S) at amino acid position 299 to be replaced by a leucine (L). 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

0.065

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.23

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.54

T;D

M_CAP

Benign

0.0082

MetaRNN

Benign

0.018

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.052

Sift

Benign

0.28

T;T

Sift4G

Benign

0.76

T;T

Polyphen

0.0

.;B

Vest4

0.13

MutPred

0.32

.;Gain of catalytic residue at D298 (P = 0.0051);

MVP

0.043

MPC

0.59

ClinPred

0.027

GERP RS

1.5

Varity_R

0.026

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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