11-62647033-C-G

Variant names:

• chr11-62647033-C-G
• rs199539004
• NM_030628.2:c.3047G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_030628.2(INTS5):​c.3047G>C​(p.Arg1016Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,610,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. R1016Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: INTS5 NM_030628.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604
• Publications: 0 publications found

Genes affected

INTS5 (HGNC:29352): (integrator complex subunit 5) The Integrator complex is a complex that associates with the C-terminal domain of RNA polymerase II large subunit. This complex is brought to U1 and U2 small nuclear RNA genes, where it is involved in the transcription and processing of their transcripts. The protein encoded by this gene represents a subunit of the Integrator complex. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09643063).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030628.2. 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
	INTS5	NM_030628.2	MANE Select	c.3047G>C	p.Arg1016Pro	missense	Exon 2 of 2	NP_085131.1	Q6P9B9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS5	ENST00000330574.2	TSL:1 MANE Select	c.3047G>C	p.Arg1016Pro	missense	Exon 2 of 2	ENSP00000327889.2	Q6P9B9

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152114 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000919 AC: 23 AN: 250180 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000384 AC: 56 AN: 1458188 Hom.: 0 Cov.: 33 AF XY: 0.0000552 AC XY: 40 AN XY: 724644

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.000177 AC: 7 AN: 39606

South Asian (SAS) AF: 0.000488 AC: 42 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1109190

Other (OTH) AF: 0.0000332 AC: 2 AN: 60166

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152232 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74430

African (AFR) AF: 0.00 AC: 0 AN: 41538

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000741 AC: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.030	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.084
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.60
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.25	T
Polyphen		0.99	D
Vest4		0.18
MutPred		0.39		Gain of glycosylation at T1019 (P = 0.0281)
MVP		0.17
MPC		0.61
ClinPred		0.14	T
GERP RS		5.4
PromoterAI		-0.00030	Neutral
Varity_R		0.48
gMVP		0.58
Mutation Taster		=79/21	polymorphism

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: rs199539004; hg19: chr11-62414505;