rs147467868

Variant names:

• chr16-58516482-G-A
• rs147467868
• NM_001160305.4:c.481G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-58516482-G-A
• chr16-58516482-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001160305.4(SETD6):​c.481G>A​(p.Glu161Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00057 in 1,614,004 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (5 hom.)
• Consequence: SETD6 NM_001160305.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.00
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• colorectal cancer

  Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011703789).
• BP6: Variant 16-58516482-G-A is Benign according to our data. Variant chr16-58516482-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2646570.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160305.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETD6	NM_001160305.4	MANE Select	c.481G>A	p.Glu161Lys	missense	Exon 4 of 8	NP_001153777.1	Q8TBK2-1
	SETD6	NM_024860.3		c.409G>A	p.Glu137Lys	missense	Exon 5 of 9	NP_079136.2	Q8TBK2-2
	SETD6	NR_134583.1		n.468G>A		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETD6	ENST00000219315.9	TSL:1 MANE Select	c.481G>A	p.Glu161Lys	missense	Exon 4 of 8	ENSP00000219315.5	Q8TBK2-1
	SETD6	ENST00000427443.5	TSL:1	n.409G>A		non_coding_transcript_exon	Exon 5 of 9	ENSP00000398033.1	E9PC53
	SETD6	ENST00000310682.6	TSL:2	c.409G>A	p.Glu137Lys	missense	Exon 5 of 9	ENSP00000310082.2	Q8TBK2-2

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152170 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000770 AC: 193 AN: 250766 AF XY: 0.000966

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00120

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000680

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000587 AC: 858 AN: 1461716 Hom.: 5 Cov.: 35 AF XY: 0.000681 AC XY: 495 AN XY: 727158

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 27 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00322 AC: 278 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5766

European-Non Finnish (NFE) AF: 0.000412 AC: 458 AN: 1111942

Other (OTH) AF: 0.000811 AC: 49 AN: 60390

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152288 Hom.: 1 Cov.: 32 AF XY: 0.000457 AC XY: 34 AN XY: 74474

African (AFR) AF: 0.0000481 AC: 2 AN: 41572

American (AMR) AF: 0.000196 AC: 3 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68010

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.000688 Hom.: 1

Bravo AF: 0.000412

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000782 AC: 95

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.00136

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.057
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N
PhyloP100		3.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.071
Sift	Benign	0.21	T
Sift4G	Benign	0.32	T
Polyphen		0.0040	B
Vest4		0.39
MVP		0.34
MPC		0.24
ClinPred		0.023	T
GERP RS		3.4
Varity_R		0.32
gMVP		0.45
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs147467868; hg19: chr16-58550386;