rs1165498065

Variant names:

• chr22-21628573-C-T
• rs1165498065
• NM_001017964.2:c.817G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-21628573-C-T
• chr22-21628573-C-A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001017964.2(YDJC):​c.817G>A​(p.Glu273Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,630 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: 6.9e-7 (0 hom.)
• Consequence: YDJC NM_001017964.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.10
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.974

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.817G>A	p.Glu273Lys	missense	Exon 5 of 5	NP_001017964.1	A8MPS7-1
	YDJC	NM_001371350.1		c.*189G>A		3_prime_UTR	Exon 4 of 4	NP_001358279.1	A8MPS7-2
	YDJC	NR_163922.1		n.884G>A		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YDJC	ENST00000292778.11	TSL:2 MANE Select	c.817G>A	p.Glu273Lys	missense	Exon 5 of 5	ENSP00000292778.6	A8MPS7-1
	YDJC	ENST00000398873.4	TSL:1	c.*189G>A		3_prime_UTR	Exon 4 of 4	ENSP00000381847.3	A8MPS7-2
	YDJC	ENST00000415762.6	TSL:1	n.*465G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000402481.2	A8MPS7-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456630 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724124

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 86014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109418

Other (OTH) AF: 0.00 AC: 0 AN: 60058

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
PhyloP100		7.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2
Varity_R		0.98
gMVP		0.99
Mutation Taster		=55/45	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1165498065; hg19: chr22-21982862;