22-21629187-C-G

Variant names:

• chr22-21629187-C-G
• rs1458816068
• NM_001017964.2:c.425G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001017964.2(YDJC):​c.425G>C​(p.Gly142Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G142V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: YDJC NM_001017964.2 missense, splice_region
• Scores: Splicing: ADA: 0.9664
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017964.2. 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
	YDJC	NM_001017964.2	MANE Select	c.425G>C	p.Gly142Ala	missense splice_region	Exon 4 of 5	NP_001017964.1	A8MPS7-1
	YDJC	NM_001371350.1		c.424+121G>C		intron	N/A	NP_001358279.1	A8MPS7-2
	YDJC	NR_163922.1		n.492G>C		splice_region non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YDJC	ENST00000292778.11	TSL:2 MANE Select	c.425G>C	p.Gly142Ala	missense splice_region	Exon 4 of 5	ENSP00000292778.6	A8MPS7-1
	YDJC	ENST00000398873.4	TSL:1	c.424+121G>C		intron	N/A	ENSP00000381847.3	A8MPS7-2
	YDJC	ENST00000415762.6	TSL:1	n.*73G>C		splice_region non_coding_transcript_exon	Exon 4 of 5	ENSP00000402481.2	A8MPS7-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1391612 Hom.: 0 Cov.: 34 AF XY: 0.00000146 AC XY: 1 AN XY: 686476

African (AFR) AF: 0.00 AC: 0 AN: 31562

American (AMR) AF: 0.00 AC: 0 AN: 35508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25008

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.00 AC: 0 AN: 79036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077934

Other (OTH) AF: 0.00 AC: 0 AN: 57872

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.013
Eigen_PC	Benign	0.033
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.065
Sift	Benign	0.47	T
Sift4G	Benign	0.70	T
Polyphen		0.73	P
Vest4		0.38
MutPred		0.55		Loss of catalytic residue at V143 (P = 0.1324)
MVP		0.28
MPC		1.2
ClinPred		0.77	D
GERP RS		3.5
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.9
Varity_R		0.19
gMVP		0.58
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.97
dbscSNV1_RF	Pathogenic	0.78
SpliceAI score (max)		0.040		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: rs1458816068; hg19: chr22-21983476;