Genetic Variant YJEFN3:p.Arg154Gly (chr19-19535367-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_198537.4(YJEFN3):c.460C>G(p.Arg154Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R154C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

YJEFN3
NM_198537.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.68

Publications

0 publications found

Variant links:

Genes affected

YJEFN3 (HGNC:24785): (YjeF N-terminal domain containing 3) Predicted to enable NADHX epimerase activity. Predicted to be involved in several processes, including hematopoietic stem cell proliferation; membrane raft distribution; and negative regulation of angiogenesis. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

YJEFN3 links:

ENSG00000258674 (HGNC:):

ENSG00000258674 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YJEFN3	NM_198537.4 link	c.460C>G	p.Arg154Gly	missense_variant	Exon 5 of 7	ENST00000514277.6	NP_940939.2	A6XGL0-1Q6ZT45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YJEFN3	ENST00000514277.6 link	c.460C>G	p.Arg154Gly	missense_variant	Exon 5 of 7	1	NM_198537.4	ENSP00000426964.1		A6XGL0-1
ENSG00000258674	ENST00000555938.1 link	c.457C>G	p.Arg153Gly	missense_variant	Exon 6 of 7	2		ENSP00000452549.1		E7ENQ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727126

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111982

Other (OTH)

AF:

0.00

AC:

AN:

60392

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

.;.;T

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

D;T;T

M_CAP

Benign

0.061

MetaRNN

Pathogenic

0.78

D;D;D

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.4

.;.;M

PhyloP100

5.7

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0050

D;T;T

Polyphen

0.90, 0.82

.;P;P

Vest4

0.75

MutPred

0.54

.;.;Loss of solvent accessibility (P = 0.0159);

MVP

0.58

MPC

0.48

ClinPred

0.96

GERP RS

3.9

Varity_R

0.74

gMVP

0.65

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.99

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over