22-21628737-G-A

Position:

• chr22-21628737-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001017964.2(YDJC):​c.653C>T​(p.Ala218Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000293 in 1,363,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: YDJC NM_001017964.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03919825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YDJC	NM_001017964.2	c.653C>T	p.Ala218Val	missense_variant	5/5	ENST00000292778.11	NP_001017964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YDJC	ENST00000292778.11	c.653C>T	p.Ala218Val	missense_variant	5/5	2	NM_001017964.2	ENSP00000292778.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000293 AC: 4 AN: 1363748 Hom.: 0 Cov.: 34 AF XY: 0.00000448 AC XY: 3 AN XY: 668958

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000264

Gnomad4 NFE exome AF: 0.00000188

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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 01, 2023

The c.653C>T (p.A218V) alteration is located in exon 5 (coding exon 5) of the YDJC gene. This alteration results from a C to T substitution at nucleotide position 653, causing the alanine (A) at amino acid position 218 to be replaced by a valine (V). 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	Benign	0.081
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.85
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	0.42	T
Polyphen		0.035	B
Vest4		0.043
MutPred		0.48		Loss of disorder (P = 0.0746);
MVP		0.014
MPC		0.67
ClinPred		0.044	T
GERP RS		0.052
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.054
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1930346261; hg19: chr22-21983026; COSMIC: COSV53037240; COSMIC: COSV53037240;