chr12-26914462-A-C

Position:

• chr12-26914462-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018164.3(INTS13):​c.1365T>G​(p.His455Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INTS13 NM_018164.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.97

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36356962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INTS13	NM_018164.3	c.1365T>G	p.His455Gln	missense_variant	12/17	ENST00000261191.12	NP_060634.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS13	ENST00000261191.12	c.1365T>G	p.His455Gln	missense_variant	12/17	1	NM_018164.3	ENSP00000261191.7
INTS13	ENST00000536232.1	c.321T>G	p.His107Gln	missense_variant	4/5	3		ENSP00000448985.1
INTS13	ENST00000538155.5	c.361-334T>G		intron_variant		5		ENSP00000445645.1
INTS13	ENST00000542392.4	n.505T>G		non_coding_transcript_exon_variant	5/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Oct 09, 2024

The c.1365T>G (p.H455Q) alteration is located in exon 12 (coding exon 11) of the ASUN gene. This alteration results from a T to G substitution at nucleotide position 1365, causing the histidine (H) at amino acid position 455 to be replaced by a glutamine (Q). 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	0.69
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.98	T
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.45	N
REVEL	Uncertain	0.29
Sift	Benign	0.39	T
Sift4G	Benign	0.31	T
Polyphen		0.99	D
Vest4		0.57
MutPred		0.48		Loss of ubiquitination at K454 (P = 0.1343);
MVP		0.11
MPC		0.69
ClinPred		0.29	T
GERP RS		-2.5
Varity_R		0.13
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-27067395;