4-139518036-T-C

Position:

• chr4-139518036-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030648.4(SETD7):​c.769A>G​(p.Ser257Gly) 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. 12/21 in silico tools predict a benign outcome for this variant. 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: 2.67

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]

SETD7 (HGNC:):

ACMG classification

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=0.30572918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD7	NM_030648.4	c.769A>G	p.Ser257Gly	missense_variant	7/8	ENST00000274031.8	NP_085151.1
SETD7	NM_001306199.2	c.769A>G	p.Ser257Gly	missense_variant	7/8		NP_001293128.1
SETD7	XM_017008661.1	c.355A>G	p.Ser119Gly	missense_variant	5/6		XP_016864150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD7	ENST00000274031.8	c.769A>G	p.Ser257Gly	missense_variant	7/8	1	NM_030648.4	ENSP00000274031.3
SETD7	ENST00000506866.6	c.769A>G	p.Ser257Gly	missense_variant	7/8	1		ENSP00000427300.1
SETD7	ENST00000515101.1	n.127A>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Sep 09, 2024

The c.769A>G (p.S257G) alteration is located in exon 7 (coding exon 7) of the SETD7 gene. This alteration results from a A to G substitution at nucleotide position 769, causing the serine (S) at amino acid position 257 to be replaced by a glycine (G). 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	0.065
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.95	N;N
REVEL	Uncertain	0.34
Sift	Benign	0.072	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.0	.;B
Vest4		0.33
MutPred		0.55		Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);
MVP		0.84
MPC		0.38
ClinPred		0.50	T
GERP RS		3.0
Varity_R		0.31
gMVP		0.34

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: chr4-140439190;