4-139529183-C-T

Position:

• chr4-139529183-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD7	NM_030648.4	c.410G>A	p.Gly137Glu	missense_variant	4/8	ENST00000274031.8	NP_085151.1
SETD7	NM_001306199.2	c.410G>A	p.Gly137Glu	missense_variant	4/8		NP_001293128.1
SETD7	XM_017008661.1	c.-5G>A		5_prime_UTR_variant	2/6		XP_016864150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD7	ENST00000274031.8	c.410G>A	p.Gly137Glu	missense_variant	4/8	1	NM_030648.4	ENSP00000274031.3
SETD7	ENST00000506866.6	c.410G>A	p.Gly137Glu	missense_variant	4/8	1		ENSP00000427300.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.410G>A (p.G137E) alteration is located in exon 4 (coding exon 4) of the SETD7 gene. This alteration results from a G to A substitution at nucleotide position 410, causing the glycine (G) at amino acid position 137 to be replaced by a glutamic acid (E). 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	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;D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Benign	0.24
Sift	Benign	0.11	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.98	.;D
Vest4		0.47
MutPred		0.51		Gain of glycosylation at T140 (P = 0.0256);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

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.

Other links and lift over

hg19: chr4-140450337;