Variant 16-58516083-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001160305.4(SETD6):c.320G>A(p.Gly107Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,416,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SETD6
NM_001160305.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0580

Variant links:

Genes affected

SETD6 (HGNC:26116): (SET domain containing 6, protein lysine methyltransferase) This gene encodes a methyltransferase that adds a methyl group to the histone H2AZ, which is involved in nuclear receptor-dependent transcription. The protein also interacts with several endogenous proteins which are involved in nuclear hormone receptor signaling. A related pseudogene is located on chromosome 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

SETD6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020309806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETD6	NM_001160305.4 linkuse as main transcript	c.320G>A	p.Gly107Asp	missense_variant	2/8	ENST00000219315.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETD6	ENST00000219315.9 linkuse as main transcript	c.320G>A	p.Gly107Asp	missense_variant	2/8	1	NM_001160305.4		Q8TBK2-1

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

148784

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:

0.000399

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000395

AC:

AN:

50682

Hom.:

AF XY:

0.0000687

AC XY:

AN XY:

29112

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:

0.000118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000485

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000189

AC:

AN:

1267814

Hom.:

Cov.:

AF XY:

0.0000209

AC XY:

AN XY:

621420

show subpopulations

Gnomad4 AFR exome

AF:

0.0000381

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000487

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000489

Gnomad4 OTH exome

AF:

0.000287

GnomAD4 genome

AF:

0.0000269

AC:

AN:

148894

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

72600

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000400

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000968

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000202

AC:

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

May 24, 2024

The c.320G>A (p.G107D) alteration is located in exon 2 (coding exon 2) of the SETD6 gene. This alteration results from a G to A substitution at nucleotide position 320, causing the glycine (G) at amino acid position 107 to be replaced by an aspartic acid (D). 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

0.073

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0063

.;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.55

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.020

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.93

.;.;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.64

N;N;N

REVEL

Benign

0.033

Sift

Benign

0.78

T;T;T

Sift4G

Benign

0.64

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.087

MutPred

0.35

.;.;Loss of helix (P = 0.0558);

MVP

0.19

MPC

0.25

ClinPred

0.042

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

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

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