12-26928859-T-G

Position:

• chr12-26928859-T-G

Variant summary

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

The NM_018164.3(INTS13):​c.347A>C​(p.Asp116Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: INTS13 NM_018164.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.18

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]

ACMG classification

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	c.347A>C	p.Asp116Ala	missense_variant	4/17	ENST00000261191.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS13	ENST00000261191.12	c.347A>C	p.Asp116Ala	missense_variant	4/17	1	NM_018164.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Jul 05, 2023

The c.347A>C (p.D116A) alteration is located in exon 4 (coding exon 3) of the ASUN gene. This alteration results from a A to C substitution at nucleotide position 347, causing the aspartic acid (D) at amino acid position 116 to be replaced by an alanine (A). 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	0.79
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T;.;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.4	N;D;D;D
REVEL	Uncertain	0.29
Sift	Benign	0.26	T;T;T;T
Sift4G	Benign	0.45	T;D;D;.
Polyphen		1.0	D;.;.;.
Vest4		0.70
MutPred		0.45		Gain of catalytic residue at S121 (P = 2e-04);.;Gain of catalytic residue at S121 (P = 2e-04);Gain of catalytic residue at S121 (P = 2e-04);
MVP		0.093
MPC		0.94
ClinPred		0.93	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1938031465; hg19: chr12-27081792;