rs148980682

Variant names:

• chr13-49482866-T-C
• rs148980682
• NM_001160308.3:c.1286T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-49482866-T-C
• chr13-49482866-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001160308.3(SETDB2):​c.1286T>C​(p.Val429Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SETDB2 NM_001160308.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48
• Publications: 0 publications found

Genes affected

SETDB2 (HGNC:20263): (SET domain bifurcated histone lysine methyltransferase 2) This gene encodes a member of a family of proteins that contain a methyl-CpG-binding domain (MBD) and a SET domain and function as histone methyltransferases. This protein is recruited to heterochromatin and plays a role in the regulation of chromosome segregation. This region is commonly deleted in chronic lymphocytic leukemia. Naturally-occuring readthrough transcription occurs from this gene to the downstream PHF11 (PHD finger protein 11) gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

SETDB2-PHF11 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.027771384).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160308.3. 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
	SETDB2	NM_001160308.3	MANE Select	c.1286T>C	p.Val429Ala	missense	Exon 9 of 14	NP_001153780.1	Q96T68-2
	SETDB2-PHF11	NM_001320727.2		c.1286T>C	p.Val429Ala	missense	Exon 9 of 20	NP_001307656.1
	SETDB2	NM_031915.3		c.1322T>C	p.Val441Ala	missense	Exon 10 of 15	NP_114121.2	Q96T68-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETDB2	ENST00000611815.2	TSL:5 MANE Select	c.1286T>C	p.Val429Ala	missense	Exon 9 of 14	ENSP00000482240.2	Q96T68-2
	SETDB2	ENST00000354234.8	TSL:1	c.1322T>C	p.Val441Ala	missense	Exon 10 of 15	ENSP00000346175.5	Q96T68-1
	SETDB2	ENST00000317257.12	TSL:1	c.1286T>C	p.Val429Ala	missense	Exon 8 of 13	ENSP00000326477.9	Q96T68-2

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251166 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461264 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 726956

African (AFR) AF: 0.000209 AC: 7 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111694

Other (OTH) AF: 0.0000166 AC: 1 AN: 60360

GnomAD4 genome AF: 0.0000853 AC: 13 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74496

African (AFR) AF: 0.000264 AC: 11 AN: 41594

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000634 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.5
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.11
Sift	Benign	0.29	T
Sift4G	Benign	0.098	T
Polyphen		0.012	B
Vest4		0.070
MVP		0.25
MPC		0.29
ClinPred		0.030	T
GERP RS		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.035
gMVP		0.58
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs148980682; hg19: chr13-50057002;