chr19-19528967-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -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. 14/22 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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
Leigh syndrome with leukodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
mitochondrial complex I deficiency, nuclear type 28
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
thyroid Hurthle cell carcinoma
Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

NDUFA13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034606814).

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.35C>T	p.Ala12Val	missense	Exon 1 of 7	NP_940939.2	A6XGL0-1
	YJEFN3	NM_001190328.2		c.35C>T	p.Ala12Val	missense	Exon 1 of 6	NP_001177257.1	A6XGL0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YJEFN3	ENST00000514277.6	TSL:1 MANE Select	c.35C>T	p.Ala12Val	missense	Exon 1 of 7	ENSP00000426964.1	A6XGL0-1
YJEFN3	ENST00000436027.9	TSL:1	c.35C>T	p.Ala12Val	missense	Exon 1 of 6	ENSP00000398520.2	A6XGL0-2
ENSG00000258674	ENST00000555938.1	TSL:2	c.315+1197C>T		intron	N/A	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

GnomAD2 exomes

AF:

0.0000265

AC:

AN:

150804

AF XY:

0.0000125

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 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

African (AFR)

AF:

0.00

AC:

AN:

31586

American (AMR)

AF:

0.000140

AC:

AN:

35680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25160

East Asian (EAS)

AF:

0.00

AC:

AN:

35728

South Asian (SAS)

AF:

0.00

AC:

AN:

79156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5436

European-Non Finnish (NFE)

AF:

0.00000371

AC:

AN:

1078764

Other (OTH)

AF:

0.00

AC:

AN:

57942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.000131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000666

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.49

M_CAP

Benign

0.0086

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

-0.15

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.31

REVEL

Benign

0.14

Sift

Benign

0.12

Sift4G

Benign

0.097

Polyphen

0.0070

Vest4

0.20

MVP

0.014

MPC

0.12

ClinPred

0.097

GERP RS

-0.33

PromoterAI

-0.092

Neutral

(source)

Varity_R

0.041

gMVP

0.099

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over