rs780657722

Variant names:

• chr1-211978405-C-G
• rs780657722
• NM_015434.4:c.1337G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-211978405-C-G
• chr1-211978405-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015434.4(INTS7):​c.1337G>C​(p.Arg446Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R446Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INTS7 NM_015434.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.88
• Publications: 2 publications found

Genes affected

INTS7 (HGNC:24484): (integrator complex subunit 7) This gene encodes a subunit of the integrator complex. The integrator complex associates with the C-terminal domain of RNA polymerase II and mediates 3'-end processing of the small nuclear RNAs U1 and U2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS7	NM_015434.4	c.1337G>C	p.Arg446Pro	missense_variant	Exon 11 of 20	ENST00000366994.8	NP_056249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS7	ENST00000366994.8	c.1337G>C	p.Arg446Pro	missense_variant	Exon 11 of 20	1	NM_015434.4	ENSP00000355961.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T;.;.;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L;L;L;.
PhyloP100		5.9
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.10	T;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		1.0	D;D;D;.
Vest4		0.96
MutPred		0.57		Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);.;
MVP		0.51
MPC		0.46
ClinPred		0.79	D
GERP RS		5.7
Varity_R		0.85
gMVP		0.78
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs780657722; hg19: chr1-212151747;