chr4-139529183-C-T

Variant names:

• chr4-139529183-C-T
• NM_030648.4:c.410G>A

Variant summary

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

The NM_030648.4(SETD7):​c.410G>A​(p.Gly137Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SETD7 NM_030648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79
• Publications: 0 publications found

Genes affected

SETD7 (HGNC:30412): (SET domain containing 7, histone lysine methyltransferase) Enables histone-lysine N-methyltransferase activity and p53 binding activity. Involved in peptidyl-lysine dimethylation and peptidyl-lysine monomethylation. Acts upstream of or within cellular response to DNA damage stimulus and heterochromatin organization. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030648.4. 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
	SETD7	NM_030648.4	MANE Select	c.410G>A	p.Gly137Glu	missense	Exon 4 of 8	NP_085151.1	Q8WTS6
	SETD7	NM_001306199.2		c.410G>A	p.Gly137Glu	missense	Exon 4 of 8	NP_001293128.1	D6RJA0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETD7	ENST00000274031.8	TSL:1 MANE Select	c.410G>A	p.Gly137Glu	missense	Exon 4 of 8	ENSP00000274031.3	Q8WTS6
	SETD7	ENST00000506866.7	TSL:1	c.410G>A	p.Gly137Glu	missense	Exon 4 of 8	ENSP00000427300.1	D6RJA0
	SETD7	ENST00000954984.1		c.410G>A	p.Gly137Glu	missense	Exon 4 of 8	ENSP00000625043.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	Pathogenic	0.97
BayesDel_addAF	Benign	-0.0047	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.8
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.24
Sift	Benign	0.11	T
Sift4G	Benign	0.28	T
Polyphen		0.98	D
Vest4		0.47
MutPred		0.51		Gain of glycosylation at T140 (P = 0.0256)
MVP		0.77
MPC		1.4
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.67
gMVP		0.91
Mutation Taster		=12/88	disease causing

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: chr4-140450337;