Variant 4-139517897-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_030648.4(SETD7):c.908G>C(p.Cys303Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SETD7
NM_030648.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.69

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_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.94

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SETD7	NM_030648.4 linkuse as main transcript	c.908G>C	p.Cys303Ser	missense_variant	7/8	ENST00000274031.8
SETD7	NM_001306199.2 linkuse as main transcript	c.908G>C	p.Cys303Ser	missense_variant	7/8
SETD7	XM_017008661.1 linkuse as main transcript	c.494G>C	p.Cys165Ser	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SETD7	ENST00000274031.8 linkuse as main transcript	c.908G>C	p.Cys303Ser	missense_variant	7/8	1	NM_030648.4	P1
SETD7	ENST00000506866.6 linkuse as main transcript	c.908G>C	p.Cys303Ser	missense_variant	7/8	1
SETD7	ENST00000515101.1 linkuse as main transcript	n.266G>C		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460832

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726684

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 09, 2023

The c.908G>C (p.C303S) alteration is located in exon 7 (coding exon 7) of the SETD7 gene. This alteration results from a G to C substitution at nucleotide position 908, causing the cysteine (C) at amino acid position 303 to be replaced by a serine (S). 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

Uncertain

0.50

BayesDel_addAF

Pathogenic

0.42

BayesDel_noAF

Pathogenic

0.36

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.035

T;T

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

T;D

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.94

D;D

MetaSVM

Uncertain

0.53

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.6

N;N

REVEL

Pathogenic

0.80

Sift

Benign

0.080

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.95

.;P

Vest4

0.93

MutPred

0.81

Gain of disorder (P = 0.0067);Gain of disorder (P = 0.0067);

MVP

0.96

MPC

1.4

ClinPred

0.87

GERP RS

5.4

Varity_R

0.60

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

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