chr19-19535367-C-T

Variant names:

• chr19-19535367-C-T
• rs1004284343
• NM_198537.4:c.460C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_198537.4(YJEFN3):​c.460C>T​(p.Arg154Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000533 in 1,613,856 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: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: YJEFN3 NM_198537.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.68
• Publications: 2 publications found

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]

ENSG00000258674 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198537.4. 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
	YJEFN3	NM_198537.4	MANE Select	c.460C>T	p.Arg154Cys	missense	Exon 5 of 7	NP_940939.2	A6XGL0-1
	YJEFN3	NM_001190328.2		c.310C>T	p.Arg104Cys	missense	Exon 4 of 6	NP_001177257.1	A6XGL0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YJEFN3	ENST00000514277.6	TSL:1 MANE Select	c.460C>T	p.Arg154Cys	missense	Exon 5 of 7	ENSP00000426964.1	A6XGL0-1
	ENSG00000258674	ENST00000555938.1	TSL:2	c.457C>T	p.Arg153Cys	missense	Exon 6 of 7	ENSP00000452549.1	E7ENQ6
	YJEFN3	ENST00000436027.9	TSL:1	c.310C>T	p.Arg104Cys	missense	Exon 4 of 6	ENSP00000398520.2	A6XGL0-2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248340 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000554 AC: 81 AN: 1461672 Hom.: 0 Cov.: 30 AF XY: 0.0000688 AC XY: 50 AN XY: 727126

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000674 AC: 75 AN: 1111982

Other (OTH) AF: 0.0000662 AC: 4 AN: 60392

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74342

African (AFR) AF: 0.0000724 AC: 3 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	Benign	0.31
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.44	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		5.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.66		Loss of solvent accessibility (P = 0.0079)
MVP		0.61
MPC		0.49
ClinPred		0.96	D
GERP RS		3.9
Varity_R		0.66
gMVP		0.69
Mutation Taster		=77/23	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

Other links and lift over

dbSNP: rs1004284343; hg19: chr19-19646176; COSMIC: COSV52278353; COSMIC: COSV52278353;