8-94827759-A-C

Position:

• chr8-94827759-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4 BP6

The NM_017864.4(INTS8):​c.484A>C​(p.Lys162Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: INTS8 NM_017864.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 6.91

Genes affected

INTS8 (HGNC:26048): (integrator complex subunit 8) This gene encodes a subunit of the Integrator complex which is involved in the cleavage of small nuclear RNAs U1 and U2 within the nucleus. The encoded protein associates with RNA polymerase II and is recruited to the U1 and U2 small nuclear RNA genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37739876).
• BP6: Variant 8-94827759-A-C is Benign according to our data. Variant chr8-94827759-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 207857.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INTS8	NM_017864.4	c.484A>C	p.Lys162Gln	missense_variant	4/27	ENST00000523731.6	NP_060334.2
INTS8	XM_047421951.1	c.484A>C	p.Lys162Gln	missense_variant	4/23		XP_047277907.1
INTS8	NR_073444.2	n.629A>C		non_coding_transcript_exon_variant	4/29
INTS8	NR_073445.2	n.629A>C		non_coding_transcript_exon_variant	4/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS8	ENST00000523731.6	c.484A>C	p.Lys162Gln	missense_variant	4/27	1	NM_017864.4	ENSP00000430338	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Benign:1

Likely benign, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.;T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.7	.;.;.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.0	D;N;D;N
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.58	.;.;.;P
Vest4		0.62
MutPred		0.38		.;.;.;Loss of methylation at K162 (P = 6e-04);
MVP		0.15
MPC		0.56
ClinPred		0.98	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.66
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs796052157; hg19: chr8-95839987;