chr19-19532634-C-T

Variant names:

• chr19-19532634-C-T
• rs2061168952
• NM_198537.4:c.212C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198537.4(YJEFN3):​c.212C>T​(p.Thr71Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,395,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: YJEFN3 NM_198537.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.823
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07201344).

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.212C>T	p.Thr71Ile	missense splice_region	Exon 3 of 7	NP_940939.2	A6XGL0-1
	YJEFN3	NM_001190328.2		c.62C>T	p.Thr21Ile	missense splice_region	Exon 2 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.212C>T	p.Thr71Ile	missense splice_region	Exon 3 of 7	ENSP00000426964.1	A6XGL0-1
	YJEFN3	ENST00000436027.9	TSL:1	c.62C>T	p.Thr21Ile	missense splice_region	Exon 2 of 6	ENSP00000398520.2	A6XGL0-2
	ENSG00000258674	ENST00000555938.1	TSL:2	c.316-2400C>T		intron	N/A	ENSP00000452549.1	E7ENQ6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1395856 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690360

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

African (AFR) AF: 0.00 AC: 0 AN: 32020

American (AMR) AF: 0.00 AC: 0 AN: 37262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25028

East Asian (EAS) AF: 0.00 AC: 0 AN: 36496

South Asian (SAS) AF: 0.00 AC: 0 AN: 79594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084374

Other (OTH) AF: 0.0000343 AC: 2 AN: 58234

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.18
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.82
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.076
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.028	D
Polyphen		0.062	B
Vest4		0.21
MutPred		0.47		Gain of helix (P = 0.0128)
MVP		0.16
MPC		0.13
ClinPred		0.69	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.11
gMVP		0.20
Mutation Taster		=90/10	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: rs2061168952; hg19: chr19-19643443;