rs149357200

Variant names:

• chr16-3656979-C-T
• rs149357200
• NM_005223.4:c.437-20C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-3656979-C-T
• chr16-3656979-C-A
• chr16-3656979-C-G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001387139.1(DNASE1):​c.486C>T​(p.His162His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000961 in 1,611,308 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00098 (3 hom.)
• Consequence: DNASE1 NM_001387139.1 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.20
• Publications: 0 publications found

Genes affected

DNASE1 (HGNC:2956): (deoxyribonuclease 1) This gene encodes a member of the DNase family. This protein is stored in the zymogen granules of the nuclear envelope and functions by cleaving DNA in an endonucleolytic manner. At least six autosomal codominant alleles have been characterized, DNASE1*1 through DNASE1*6, and the sequence of DNASE1*2 represented in this record. Mutations in this gene have been associated with systemic lupus erythematosus (SLE), an autoimmune disease. A recombinant form of this protein is used to treat the one of the symptoms of cystic fibrosis by hydrolyzing the extracellular DNA in sputum and reducing its viscosity. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

LOC124903631 (HGNC:):

TRAP1 (HGNC:16264): (TNF receptor associated protein 1) This gene encodes a mitochondrial chaperone protein that is member of the heat shock protein 90 (HSP90) family. The encoded protein has ATPase activity and interacts with tumor necrosis factor type I. This protein may function in regulating cellular stress responses. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

TRAP1 Gene-Disease associations (from GenCC):

• syndromic disease

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-1.2 with no splicing effect.
• BS2: High AC in GnomAd4 at 117 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387139.1. 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
	DNASE1	NM_005223.4	MANE Select	c.437-20C>T		intron	N/A	NP_005214.2
	DNASE1	NM_001387139.1		c.486C>T	p.His162His	synonymous	Exon 6 of 9	NP_001374068.1
	DNASE1	NM_001351825.2		c.437-20C>T		intron	N/A	NP_001338754.1	P24855-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNASE1	ENST00000246949.10	TSL:1 MANE Select	c.437-20C>T		intron	N/A	ENSP00000246949.5	P24855-1
	DNASE1	ENST00000407479.5	TSL:1	c.437-20C>T		intron	N/A	ENSP00000385905.1	P24855-1
	DNASE1	ENST00000570664.1	TSL:5	c.44-20C>T		intron	N/A	ENSP00000459507.1	I3L298

Frequencies

GnomAD3 genomes AF: 0.000769 AC: 117 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000720 AC: 176 AN: 244524 AF XY: 0.000694

Gnomad AFR exome AF: 0.000383

Gnomad AMR exome AF: 0.00120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000552

Gnomad FIN exome AF: 0.000744

Gnomad NFE exome AF: 0.000950

Gnomad OTH exome AF: 0.00134

GnomAD4 exome AF: 0.000981 AC: 1432 AN: 1459000 Hom.: 3 Cov.: 32 AF XY: 0.000927 AC XY: 673 AN XY: 725650

African (AFR) AF: 0.000149 AC: 5 AN: 33448

American (AMR) AF: 0.00122 AC: 54 AN: 44338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39630

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85804

European-Finnish (FIN) AF: 0.000684 AC: 36 AN: 52642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00116 AC: 1284 AN: 1111022

Other (OTH) AF: 0.000813 AC: 49 AN: 60288

GnomAD4 genome AF: 0.000768 AC: 117 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000725 AC XY: 54 AN XY: 74466

African (AFR) AF: 0.000433 AC: 18 AN: 41566

American (AMR) AF: 0.00137 AC: 21 AN: 15308

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00109 AC: 74 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000251 Hom.: 0

Bravo AF: 0.000759

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.85
PhyloP100		-1.2
PromoterAI		0.12	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs149357200; hg19: chr16-3706980;