Genetic Variant YDJC:p.Arg270Trp (chr22-21628582-G-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001017964.2(YDJC):c.808C>T(p.Arg270Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,455,168 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R270Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

YDJC
NM_001017964.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

Publications

4 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.972

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YDJC	NM_001017964.2	MANE Select	c.808C>T	p.Arg270Trp	missense	Exon 5 of 5	NP_001017964.1	A8MPS7-1
YDJC	NM_001371350.1		c.*180C>T		3_prime_UTR	Exon 4 of 4	NP_001358279.1	A8MPS7-2
YDJC	NR_163922.1		n.875C>T		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YDJC	ENST00000292778.11	TSL:2 MANE Select	c.808C>T	p.Arg270Trp	missense	Exon 5 of 5	ENSP00000292778.6	A8MPS7-1
YDJC	ENST00000398873.4	TSL:1	c.*180C>T		3_prime_UTR	Exon 4 of 4	ENSP00000381847.3	A8MPS7-2
YDJC	ENST00000415762.6	TSL:1	n.*456C>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000402481.2	A8MPS7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000335

AC:

AN:

238810

AF XY:

0.0000459

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000394

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000942

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1455168

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

723214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33354

American (AMR)

AF:

0.00

AC:

AN:

44136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26010

East Asian (EAS)

AF:

0.000253

AC:

AN:

39520

South Asian (SAS)

AF:

0.00

AC:

AN:

85916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00000541

AC:

AN:

1108610

Other (OTH)

AF:

0.0000167

AC:

AN:

60042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000331

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.97

MetaSVM

Uncertain

-0.018

MutationAssessor

Uncertain

2.3

PhyloP100

2.8

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-6.0

REVEL

Pathogenic

0.68

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.94

MutPred

0.94

Loss of disorder (P = 0.0716)

MVP

0.62

MPC

1.7

ClinPred

0.91

GERP RS

0.61

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.3

Varity_R

0.80

gMVP

0.97

Mutation Taster

=37/63

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over