19-19535408-C-A

Variant names:

• chr19-19535408-C-A
• rs141151340
• NM_198537.4:c.501C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_198537.4(YJEFN3):​c.501C>A​(p.Cys167*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,714 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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: YJEFN3 NM_198537.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.994
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.501C>A	p.Cys167*	stop_gained	Exon 5 of 7	NP_940939.2	A6XGL0-1
	YJEFN3	NM_001190328.2		c.351C>A	p.Cys117*	stop_gained	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.501C>A	p.Cys167*	stop_gained	Exon 5 of 7	ENSP00000426964.1	A6XGL0-1
	ENSG00000258674	ENST00000555938.1	TSL:2	c.498C>A	p.Cys166*	stop_gained	Exon 6 of 7	ENSP00000452549.1	E7ENQ6
	YJEFN3	ENST00000436027.9	TSL:1	c.351C>A	p.Cys117*	stop_gained	Exon 4 of 6	ENSP00000398520.2	A6XGL0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461714 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727162

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

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: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53292

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

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	27
DANN	Benign	0.97
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.25	N
PhyloP100		-0.99
Vest4		0.43
GERP RS		-6.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=42/158	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs141151340; hg19: chr19-19646217;