NM_001366418.1:c.1238A>G

Variant names:

• chr1-150946983-A-G
• NM_001366418.1:c.1238A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366418.1(SETDB1):​c.1238A>G​(p.Gln413Arg) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SETDB1 NM_001366418.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14744124).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366418.1. 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
	SETDB1	NM_001366418.1	MANE Select	c.1238A>G	p.Gln413Arg	missense	Exon 10 of 22	NP_001353347.1	A0A8I5KT93
	SETDB1	NM_001366417.1		c.1238A>G	p.Gln413Arg	missense	Exon 10 of 22	NP_001353346.1	A0A8I5KT93
	SETDB1	NM_001393958.1		c.1238A>G	p.Gln413Arg	missense	Exon 10 of 22	NP_001380887.1	A0A8I5KT93

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETDB1	ENST00000692827.1	MANE Select	c.1238A>G	p.Gln413Arg	missense	Exon 10 of 22	ENSP00000509425.1	A0A8I5KT93
	SETDB1	ENST00000271640.9	TSL:1	c.1238A>G	p.Gln413Arg	missense	Exon 10 of 22	ENSP00000271640.5	Q15047-1
	SETDB1	ENST00000368969.8	TSL:1	c.1238A>G	p.Gln413Arg	missense	Exon 10 of 22	ENSP00000357965.4	Q15047-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.0067	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T
Eigen	Benign	-0.053
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.061
Sift	Benign	0.21	T
Sift4G	Benign	0.21	T
Polyphen		0.023	B
Vest4		0.21
MutPred		0.15		Gain of MoRF binding (P = 0.039)
MVP		0.80
MPC		1.4
ClinPred		0.63	D
GERP RS		5.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.059
gMVP		0.48
Mutation Taster		=84/16	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

hg19: chr1-150919459;