Variant 4-139517893-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_030648.4(SETD7):c.912C>G(p.Ile304Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,613,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

SETD7
NM_030648.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22693747).

BS2

High AC in GnomAd4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SETD7	NM_030648.4 linkuse as main transcript	c.912C>G	p.Ile304Met	missense_variant	7/8	ENST00000274031.8
SETD7	NM_001306199.2 linkuse as main transcript	c.912C>G	p.Ile304Met	missense_variant	7/8
SETD7	XM_017008661.1 linkuse as main transcript	c.498C>G	p.Ile166Met	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SETD7	ENST00000274031.8 linkuse as main transcript	c.912C>G	p.Ile304Met	missense_variant	7/8	1	NM_030648.4	P1
SETD7	ENST00000506866.6 linkuse as main transcript	c.912C>G	p.Ile304Met	missense_variant	7/8	1
SETD7	ENST00000515101.1 linkuse as main transcript	n.270C>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

250040

Hom.:

AF XY:

0.0000814

AC XY:

AN XY:

135096

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000204

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000199

AC:

291

AN:

1461038

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

134

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.000112

Gnomad4 NFE exome

AF:

0.000252

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000164

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000156

Hom.:

Bravo

AF:

0.000178

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.912C>G (p.I304M) alteration is located in exon 7 (coding exon 7) of the SETD7 gene. This alteration results from a C to G substitution at nucleotide position 912, causing the isoleucine (I) at amino acid position 304 to be replaced by a methionine (M). 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

0.070

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.074

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.39

MutationAssessor

Benign

1.0

.;L

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.050

N;N

REVEL

Benign

0.24

Sift

Benign

0.13

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.0020

.;B

Vest4

0.38

MVP

0.86

MPC

0.43

ClinPred

0.081

GERP RS

4.5

Varity_R

0.17

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over