4-139556118-A-G

Position:

• chr4-139556118-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030648.4(SETD7):​c.20T>C​(p.Met7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,452,276 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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: 33)
  • Exomes 𝑓: 0.0000028 (1 hom.)
• Consequence: SETD7 NM_030648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.058093786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD7	NM_030648.4	c.20T>C	p.Met7Thr	missense_variant	1/8	ENST00000274031.8	NP_085151.1
SETD7	NM_001306199.2	c.20T>C	p.Met7Thr	missense_variant	1/8		NP_001293128.1
SETD7	NM_001306200.2	c.20T>C	p.Met7Thr	missense_variant	1/3		NP_001293129.1
SETD7	NR_131339.2	n.102T>C		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD7	ENST00000274031.8	c.20T>C	p.Met7Thr	missense_variant	1/8	1	NM_030648.4	ENSP00000274031.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1452276 Hom.: 1 Cov.: 30 AF XY: 0.00000416 AC XY: 3 AN XY: 721906

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Aug 26, 2024

The c.20T>C (p.M7T) alteration is located in exon 1 (coding exon 1) of the SETD7 gene. This alteration results from a T to C substitution at nucleotide position 20, causing the methionine (M) at amino acid position 7 to be replaced by a threonine (T). 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	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Benign	0.84
DEOGEN2	Benign	0.013	T;T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.41	.;N;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.030	N;N;N
REVEL	Benign	0.018
Sift	Benign	0.43	T;T;T
Sift4G	Benign	0.68	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.26
MutPred		0.30		Gain of glycosylation at S3 (P = 0.0111);Gain of glycosylation at S3 (P = 0.0111);Gain of glycosylation at S3 (P = 0.0111);
MVP		0.27
MPC		0.48
ClinPred		0.10	T
GERP RS		3.2
Varity_R		0.076
gMVP		0.14

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: chr4-140477272;