13-49468348-T-G

Variant names:

• chr13-49468348-T-G
• rs9316454
• NM_001160308.3:c.305+388T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001160308.3(SETDB2):​c.305+388T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,876 control chromosomes in the GnomAD database, including 17,002 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (17002 hom., cov: 31)
• Consequence: SETDB2 NM_001160308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

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.305+388T>G		intron	N/A	NP_001153780.1	Q96T68-2
	SETDB2-PHF11	NM_001320727.2		c.305+388T>G		intron	N/A	NP_001307656.1
	SETDB2	NM_031915.3		c.341+388T>G		intron	N/A	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.305+388T>G		intron	N/A	ENSP00000482240.2	Q96T68-2
	SETDB2	ENST00000354234.8	TSL:1	c.341+388T>G		intron	N/A	ENSP00000346175.5	Q96T68-1
	SETDB2	ENST00000317257.12	TSL:1	c.305+388T>G		intron	N/A	ENSP00000326477.9	Q96T68-2

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70338 AN: 151756 Hom.: 16991 Cov.: 31

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.496

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.463 AC: 70364 AN: 151876 Hom.: 17002 Cov.: 31 AF XY: 0.459 AC XY: 34049 AN XY: 74218

African (AFR) AF: 0.327 AC: 13570 AN: 41450

American (AMR) AF: 0.493 AC: 7529 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1772 AN: 3468

East Asian (EAS) AF: 0.456 AC: 2352 AN: 5154

South Asian (SAS) AF: 0.323 AC: 1559 AN: 4820

European-Finnish (FIN) AF: 0.495 AC: 5208 AN: 10518

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36740 AN: 67876

Other (OTH) AF: 0.494 AC: 1043 AN: 2110

Alfa AF: 0.507 Hom.: 9588

Bravo AF: 0.462

Asia WGS AF: 0.373 AC: 1293 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.57
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs9316454; hg19: chr13-50042484;