Variant 1-150941367-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001366418.1(SETDB1):c.486A>C(p.Gln162His) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SETDB1
NM_001366418.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.402

Variant links:

Genes affected

SETDB1 (HGNC:10761): (SET domain bifurcated histone lysine methyltransferase 1) This gene encodes a histone methyltransferase which regulates histone methylation, gene silencing, and transcriptional repression. This gene has been identified as a target for treatment in Huntington Disease, given that gene silencing and transcription dysfunction likely play a role in the disease pathogenesis. Alternatively spliced transcript variants of this gene have been described.[provided by RefSeq, Jun 2011]

SETDB1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27689052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETDB1	NM_001366418.1 linkuse as main transcript	c.486A>C	p.Gln162His	missense_variant	5/22	ENST00000692827.1	NP_001353347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETDB1	ENST00000692827.1 linkuse as main transcript	c.486A>C	p.Gln162His	missense_variant	5/22		NM_001366418.1	ENSP00000509425	A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.486A>C (p.Q162H) alteration is located in exon 5 (coding exon 4) of the SETDB1 gene. This alteration results from a A to C substitution at nucleotide position 486, causing the glutamine (Q) at amino acid position 162 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Uncertain

0.096

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;T;.;T;.;.;T

Eigen

Benign

-0.073

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.84

T;T;T;T;T;D;T

M_CAP

Benign

0.078

MetaRNN

Benign

0.28

T;T;T;T;T;T;T

MetaSVM

Uncertain

0.033

MutationAssessor

Benign

1.7

.;L;L;.;L;.;.

MutationTaster

Benign

0.70

D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.6

D;N;N;N;N;D;N

REVEL

Uncertain

0.31

Sift

Uncertain

0.0030

D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Polyphen

0.99, 1.0, 1.0, 0.99, 1.0

.;D;D;D;D;.;D

Vest4

0.29, 0.27, 0.27, 0.34

MutPred

0.14

Loss of ubiquitination at K159 (P = 0.0503);Loss of ubiquitination at K159 (P = 0.0503);Loss of ubiquitination at K159 (P = 0.0503);Loss of ubiquitination at K159 (P = 0.0503);Loss of ubiquitination at K159 (P = 0.0503);Loss of ubiquitination at K159 (P = 0.0503);Loss of ubiquitination at K159 (P = 0.0503);

MVP

0.93

MPC

0.61

ClinPred

0.94

GERP RS

-2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.55

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over