rs932999699

Variant names:

• chr1-1312098-C-G
• rs932999699
• NM_017871.6:c.1657G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-1312098-C-G
• chr1-1312098-C-T

Variant summary

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

The NM_017871.6(INTS11):​c.1657G>C​(p.Val553Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,906 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V553M) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: INTS11 NM_017871.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.20

Genes affected

INTS11 (HGNC:26052): (integrator complex subunit 11) The Integrator complex contains at least 12 subunits and associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates the 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690). INTS11, or CPSF3L, is the catalytic subunit of the Integrator complex (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

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 rank	MANE	Protein	UniProt
INTS11	NM_017871.6	c.1657G>C	p.Val553Leu	missense_variant	Exon 16 of 17	ENST00000435064.6	NP_060341.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS11	ENST00000435064.6	c.1657G>C	p.Val553Leu	missense_variant	Exon 16 of 17	1	NM_017871.6	ENSP00000413493.2

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150906 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150906 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73588

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.025	.;.;.;T;T;T;.;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;.;.;.;L;.;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.45	N;N;.;.;N;N;.;N;N
REVEL	Benign	0.19
Sift	Benign	0.21	T;T;.;.;T;T;.;T;T
Sift4G	Benign	0.32	T;T;T;T;T;T;T;T;T
Polyphen		0.0040, 0.0070, 0.0030	.;.;.;.;B;B;.;B;B
Vest4		0.78
MutPred		0.48		.;.;.;.;Gain of sheet (P = 0.1451);.;.;.;.;
MVP		0.55
MPC		0.033
ClinPred		0.62	D
GERP RS		3.1
Varity_R		0.25
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs932999699; hg19: chr1-1247478;