12-26911217-C-T

Position:

• chr12-26911217-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018164.3(INTS13):​c.1906G>A​(p.Val636Ile) 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. 14/20 in silico tools predict a benign outcome for this variant. 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: 0.105

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 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=0.040700227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS13	NM_018164.3	c.1906G>A	p.Val636Ile	missense_variant	15/17	ENST00000261191.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS13	ENST00000261191.12	c.1906G>A	p.Val636Ile	missense_variant	15/17	1	NM_018164.3	P1
INTS13	ENST00000538155.5	c.847G>A	p.Val283Ile	missense_variant	6/8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jan 26, 2022

The c.1906G>A (p.V636I) alteration is located in exon 15 (coding exon 14) of the ASUN gene. This alteration results from a G to A substitution at nucleotide position 1906, causing the valine (V) at amino acid position 636 to be replaced by an isoleucine (I). 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	0.064
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Benign	0.91
DEOGEN2	Benign	0.0083	T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.89	D;D
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.091
Sift	Benign	0.53	T;T
Sift4G	Benign	0.55	T;T
Polyphen		0.0	.;B
Vest4		0.036
MutPred		0.42		.;Loss of sheet (P = 0.0817);
MVP		0.043
MPC		0.54
ClinPred		0.36	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.051

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

Other links and lift over

dbSNP: rs751914935; hg19: chr12-27064150;