4-139533236-C-G

Variant names:

• chr4-139533236-C-G
• NM_030648.4:c.301G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030648.4(SETD7):​c.301G>C​(p.Asp101His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SETD7 NM_030648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.39

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 rank	MANE	Protein	UniProt
SETD7	NM_030648.4	c.301G>C	p.Asp101His	missense_variant	Exon 3 of 8	ENST00000274031.8	NP_085151.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETD7	ENST00000274031.8	c.301G>C	p.Asp101His	missense_variant	Exon 3 of 8	1	NM_030648.4	ENSP00000274031.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.301G>C (p.D101H) alteration is located in exon 3 (coding exon 3) of the SETD7 gene. This alteration results from a G to C substitution at nucleotide position 301, causing the aspartic acid (D) at amino acid position 101 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	0.18
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;D;T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.73	D;D;D;D
MetaSVM	Benign	-0.32	T
MutationAssessor	Pathogenic	3.0	.;M;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.3	D;D;D;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.0080	D;D;D;.
Sift4G	Uncertain	0.021	D;D;D;D
Polyphen		0.95, 0.99	.;P;D;.
Vest4		0.55
MutPred		0.68		Gain of glycosylation at T100 (P = 0.037);Gain of glycosylation at T100 (P = 0.037);Gain of glycosylation at T100 (P = 0.037);.;
MVP		0.82
MPC		0.63
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.40
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr4-140454390;