Variant 12-26924432-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018164.3(INTS13):c.727C>G(p.Leu243Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000089 in 1,461,080 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

INTS13
NM_018164.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.82

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS13	NM_018164.3 linkuse as main transcript	c.727C>G	p.Leu243Val	missense_variant	7/17	ENST00000261191.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS13	ENST00000261191.12 linkuse as main transcript	c.727C>G	p.Leu243Val	missense_variant	7/17	1	NM_018164.3	P1	Q9NVM9-1
INTS13	ENST00000536232.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250766

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135522

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461080

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726824

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000345

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.000165

Hom.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.0000593

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

Mar 07, 2023

The c.727C>G (p.L243V) alteration is located in exon 7 (coding exon 6) of the ASUN gene. This alteration results from a C to G substitution at nucleotide position 727, causing the leucine (L) at amino acid position 243 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

Benign

0.25

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.80

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.4

REVEL

Benign

0.22

Sift

Uncertain

0.013

Sift4G

Uncertain

0.048

Polyphen

0.16

Vest4

0.78

MutPred

0.64

Gain of catalytic residue at K246 (P = 0);

MVP

0.53

MPC

0.76

ClinPred

0.19

GERP RS

5.0

Varity_R

0.63

gMVP

0.54

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

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