19-19528967-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198537.4(YJEFN3):c.35C>T(p.Ala12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000774 in 1,550,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

YJEFN3
NM_198537.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.148

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:

NDUFA13 (HGNC:17194): (NADH:ubiquinone oxidoreductase subunit A13) This gene encodes a subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), which functions in the transfer of electrons from NADH to the respiratory chain. The protein is required for complex I assembly and electron transfer activity. The protein binds the signal transducers and activators of transcription 3 (STAT3) transcription factor, and can function as a tumor suppressor. The human protein purified from mitochondria migrates at approximately 16 kDa. Transcripts originating from an upstream promoter and capable of expressing a protein with a longer N-terminus have been found, but their biological validity has not been determined. [provided by RefSeq, Oct 2009]

NDUFA13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.034606814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YJEFN3	NM_198537.4 link	c.35C>T	p.Ala12Val	missense_variant	Exon 1 of 7	ENST00000514277.6	NP_940939.2	A6XGL0-1Q6ZT45
YJEFN3	NM_001190328.2 link	c.35C>T	p.Ala12Val	missense_variant	Exon 1 of 6		NP_001177257.1	A6XGL0-2
YJEFN3	XM_005259903.5 link	c.-119C>T		5_prime_UTR_variant	Exon 1 of 6		XP_005259960.1
YJEFN3	XM_011527996.3 link	c.-119C>T		5_prime_UTR_variant	Exon 1 of 3		XP_011526298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YJEFN3	ENST00000514277.6 link	c.35C>T	p.Ala12Val	missense_variant	Exon 1 of 7	1	NM_198537.4	ENSP00000426964.1		A6XGL0-1
ENSG00000258674	ENST00000555938.1 link	c.315+1197C>T		intron_variant	Intron 4 of 6	2		ENSP00000452549.1		E7ENQ6

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000265

AC:

AN:

150804

Hom.:

AF XY:

0.0000125

AC XY:

AN XY:

80274

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000644

AC:

AN:

1397920

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689382

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000666

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.35C>T (p.A12V) alteration is located in exon 1 (coding exon 1) of the YJEFN3 gene. This alteration results from a C to T substitution at nucleotide position 35, causing the alanine (A) at amino acid position 12 to be replaced by a valine (V). 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

0.095

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

.;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.31

N;N

REVEL

Benign

0.14

Sift

Benign

0.12

T;D

Sift4G

Benign

0.097

T;D

Polyphen

0.0070

B;B

Vest4

0.20

MVP

0.014

MPC

0.12

ClinPred

0.097

GERP RS

-0.33

Varity_R

0.041

gMVP

0.099

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over