rs11697186

Variant names:

• chr20-3204477-A-C
• rs11697186
• NM_023935.3:c.91+60T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-3204477-A-C
• chr20-3204477-A-G
• chr20-3204477-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_023935.3(DDRGK1):​c.91+60T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: DDRGK1 NM_023935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922
• Publications: 32 publications found

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:6176): (inosine triphosphatase) This gene encodes an inosine triphosphate pyrophosphohydrolase. The encoded protein hydrolyzes inosine triphosphate and deoxyinosine triphosphate to the monophosphate nucleotide and diphosphate. This protein, which is a member of the HAM1 NTPase protein family, is found in the cytoplasm and acts as a homodimer. Defects in the encoded protein can result in inosine triphosphate pyrophosphorylase deficiency which causes an accumulation of ITP in red blood cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ITPA Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 35

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• inosine triphosphatase deficiency

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000303521 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023935.3. 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
	DDRGK1	NM_023935.3	MANE Select	c.91+60T>G		intron	N/A	NP_076424.1	Q96HY6-1
	ITPA	NM_001424409.1		c.-126+198A>C		intron	N/A	NP_001411338.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDRGK1	ENST00000354488.8	TSL:1 MANE Select	c.91+60T>G		intron	N/A	ENSP00000346483.3	Q96HY6-1
	DDRGK1	ENST00000897092.1		c.91+60T>G		intron	N/A	ENSP00000567151.1
	DDRGK1	ENST00000941356.1		c.91+60T>G		intron	N/A	ENSP00000611415.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.61
PhyloP100		-0.92
PromoterAI		-0.051	Neutral

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: rs11697186; hg19: chr20-3185123;