22-21629640-G-A

Position:

• chr22-21629640-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001017964.2(YDJC):​c.286C>T​(p.Arg96Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: YDJC NM_001017964.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29

Genes affected

YDJC (HGNC:27158): (YdjC chitooligosaccharide deacetylase homolog) Predicted to enable deacetylase activity and magnesium ion binding activity. Predicted to be involved in carbohydrate metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

YDJC (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YDJC	NM_001017964.2	c.286C>T	p.Arg96Trp	missense_variant	2/5	ENST00000292778.11	NP_001017964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YDJC	ENST00000292778.11	c.286C>T	p.Arg96Trp	missense_variant	2/5	2	NM_001017964.2	ENSP00000292778.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460196 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726398

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.286C>T (p.R96W) alteration is located in exon 2 (coding exon 2) of the YDJC gene. This alteration results from a C to T substitution at nucleotide position 286, causing the arginine (R) at amino acid position 96 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.6	D;N
REVEL	Benign	0.22
Sift	Benign	0.086	T;T
Sift4G	Uncertain	0.036	D;T
Polyphen		0.98	D;D
Vest4		0.90
MutPred		0.73		Loss of disorder (P = 0.0023);Loss of disorder (P = 0.0023);
MVP		0.45
MPC		1.0
ClinPred		0.98	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.53
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs962594748; hg19: chr22-21983929;