20-3204477-A-T

Position:

• chr20-3204477-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023935.3(DDRGK1):​c.91+60T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 1,507,878 control chromosomes in the GnomAD database, including 5,062 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 0.071 (450 hom., cov: 32)
  • Exomes 𝑓: 0.078 (4612 hom.)
• Consequence: DDRGK1 NM_023935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922

Genes affected

DDRGK1 (HGNC:16110): (DDRGK domain containing 1) The protein encoded by this gene interacts with components of the ubiquitin fold modifier 1 conjugation pathway and helps prevent apoptosis in ER-stressed secretory tissues. In addition, the encoded protein regulates nuclear factor-κB activity. [provided by RefSeq, Dec 2015]

ITPA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDRGK1	NM_023935.3	c.91+60T>A		intron_variant		ENST00000354488.8	NP_076424.1
ITPA	XM_047440139.1	c.-126+198A>T		intron_variant			XP_047296095.1
ITPA	XM_047440140.1	c.-126+198A>T		intron_variant			XP_047296096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDRGK1	ENST00000354488.8	c.91+60T>A		intron_variant		1	NM_023935.3	ENSP00000346483	P1
DDRGK1	ENST00000380201.2	c.91+60T>A		intron_variant		2		ENSP00000369548

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10834 AN: 152130 Hom.: 452 Cov.: 32

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0394

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0483

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0728

Gnomad OTH AF: 0.0670

GnomAD4 exome AF: 0.0781 AC: 105864 AN: 1355630 Hom.: 4612 AF XY: 0.0797 AC XY: 53428 AN XY: 670410

Gnomad4 AFR exome AF: 0.0671

Gnomad4 AMR exome AF: 0.0326

Gnomad4 ASJ exome AF: 0.0725

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0596

Gnomad4 NFE exome AF: 0.0740

Gnomad4 OTH exome AF: 0.0809

GnomAD4 genome AF: 0.0712 AC: 10836 AN: 152248 Hom.: 450 Cov.: 32 AF XY: 0.0713 AC XY: 5310 AN XY: 74428

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.0394

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0483

Gnomad4 NFE AF: 0.0728

Gnomad4 OTH AF: 0.0658

Alfa AF: 0.0763 Hom.: 306

Bravo AF: 0.0684

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.1
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs11697186; hg19: chr20-3185123;