19-19529434-C-T

Variant names:

• chr19-19529434-C-T
• rs1159655320
• NM_198537.4:c.130C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198537.4(YJEFN3):​c.130C>T​(p.Leu44Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: YJEFN3 NM_198537.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.272

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05515206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YJEFN3	NM_198537.4	c.130C>T	p.Leu44Phe	missense_variant	Exon 2 of 7	ENST00000514277.6	NP_940939.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YJEFN3	ENST00000514277.6	c.130C>T	p.Leu44Phe	missense_variant	Exon 2 of 7	1	NM_198537.4	ENSP00000426964.1
ENSG00000258674	ENST00000555938.1	c.315+1664C>T		intron_variant	Intron 4 of 6	2		ENSP00000452549.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.130C>T (p.L44F) alteration is located in exon 2 (coding exon 2) of the YJEFN3 gene. This alteration results from a C to T substitution at nucleotide position 130, causing the leucine (L) at amino acid position 44 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.86
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.023
Sift	Benign	0.33	T
Sift4G	Benign	0.066	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.29		Loss of MoRF binding (P = 0.1236);
MVP		0.014
MPC		0.13
ClinPred		0.086	T
GERP RS		0.61
Varity_R		0.055
gMVP		0.078

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1159655320; hg19: chr19-19640243; COSMIC: COSV53063480; COSMIC: COSV53063480;