rs2306852

Variant names:

• chr12-26936607-A-G
• rs2306852
• NM_018164.3:c.197T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018164.3(INTS13):​c.197T>C​(p.Met66Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 1,611,946 control chromosomes in the GnomAD database, including 58 homozygotes. 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: 𝑓 0.0051 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (54 hom.)
• Consequence: INTS13 NM_018164.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.87
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009756386).
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018164.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS13	NM_018164.3	MANE Select	c.197T>C	p.Met66Thr	missense	Exon 2 of 17	NP_060634.2	Q9NVM9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS13	ENST00000261191.12	TSL:1 MANE Select	c.197T>C	p.Met66Thr	missense	Exon 2 of 17	ENSP00000261191.7	Q9NVM9-1
	INTS13	ENST00000892608.1		c.197T>C	p.Met66Thr	missense	Exon 2 of 17	ENSP00000562667.1
	INTS13	ENST00000892612.1		c.197T>C	p.Met66Thr	missense	Exon 3 of 18	ENSP00000562671.1

Frequencies

GnomAD3 genomes AF: 0.00512 AC: 780 AN: 152208 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00620

Gnomad OTH AF: 0.00525

GnomAD2 exomes AF: 0.00706 AC: 1775 AN: 251278 AF XY: 0.00756

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.00824

Gnomad EAS exome AF: 0.00310

Gnomad FIN exome AF: 0.0142

Gnomad NFE exome AF: 0.00690

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00659 AC: 9619 AN: 1459620 Hom.: 54 Cov.: 31 AF XY: 0.00680 AC XY: 4941 AN XY: 726176

African (AFR) AF: 0.000957 AC: 32 AN: 33426

American (AMR) AF: 0.00333 AC: 149 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00819 AC: 214 AN: 26122

East Asian (EAS) AF: 0.00592 AC: 235 AN: 39674

South Asian (SAS) AF: 0.0116 AC: 998 AN: 86186

European-Finnish (FIN) AF: 0.0129 AC: 691 AN: 53360

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5764

European-Non Finnish (NFE) AF: 0.00624 AC: 6929 AN: 1110040

Other (OTH) AF: 0.00583 AC: 352 AN: 60330

GnomAD4 genome AF: 0.00511 AC: 779 AN: 152326 Hom.: 4 Cov.: 32 AF XY: 0.00580 AC XY: 432 AN XY: 74478

African (AFR) AF: 0.000914 AC: 38 AN: 41564

American (AMR) AF: 0.00229 AC: 35 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5186

South Asian (SAS) AF: 0.0166 AC: 80 AN: 4830

European-Finnish (FIN) AF: 0.0135 AC: 143 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00620 AC: 422 AN: 68030

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00595 Hom.: 8

Bravo AF: 0.00385

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00674 AC: 58

ExAC AF: 0.00733 AC: 890

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.00643

EpiControl AF: 0.00717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.049	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0098	T
MetaSVM	Benign	-1.0	T
PhyloP100		8.9
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.26
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.019	D
Polyphen		0.37	B
Vest4		0.64
MVP		0.043
MPC		0.94
ClinPred		0.022	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.58
gMVP		0.75
Mutation Taster		=40/60	disease causing

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

Other links and lift over

dbSNP: rs2306852; hg19: chr12-27089540; COSMIC: COSV105033588; COSMIC: COSV105033588;