Genetic Variant ENOSF1:p.Pro439Pro (chr18-674320-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_017512.7(ENOSF1):c.1317T>C(p.Pro439Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 1,608,890 control chromosomes in the GnomAD database, including 9,322 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.092 ( 814 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8508 hom. )

Consequence

ENOSF1
NM_017512.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.52

Publications

29 publications found

Variant links:

Genes affected

ENOSF1 (HGNC:30365): (enolase superfamily member 1) This gene can encode a mitochondrial enzyme that is thought to convert L-fuconate to 2-keto-3-deoxy-L-fuconate. This locus was originally identified as the source of antisense RNAs of the adjacent thymidylate synthase gene. Splice variants at this locus may contain an alternate 3' exon that is complementary to the 3'UTR and terminal intron of the thymidylate synthase (TS) RNA and may downregulate TS expression. [provided by RefSeq, Aug 2017]

ENOSF1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP7

Synonymous conserved (PhyloP=1.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENOSF1	NM_017512.7 link	c.1317T>C	p.Pro439Pro	synonymous_variant	Exon 16 of 16	ENST00000647584.2	NP_059982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584.2 link	c.1317T>C	p.Pro439Pro	synonymous_variant	Exon 16 of 16		NM_017512.7	ENSP00000497230.2

Frequencies

GnomAD3 genomes

AF:

0.0923

AC:

14029

AN:

152042

Hom.:

815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0306

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.0772

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0960

Gnomad OTH

AF:

0.0895

GnomAD2 exomes

AF:

0.116

AC:

28621

AN:

247214

AF XY:

0.111

show subpopulations

Gnomad AFR exome

AF:

0.0297

Gnomad AMR exome

AF:

0.227

Gnomad ASJ exome

AF:

0.0869

Gnomad EAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.0937

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.101

AC:

146715

AN:

1456730

Hom.:

8508

Cov.:

AF XY:

0.100

AC XY:

72734

AN XY:

724750

show subpopulations

African (AFR)

AF:

0.0293

AC:

969

AN:

33124

American (AMR)

AF:

0.223

AC:

9790

AN:

43974

Ashkenazi Jewish (ASJ)

AF:

0.0849

AC:

2211

AN:

26028

East Asian (EAS)

AF:

0.191

AC:

7522

AN:

39390

South Asian (SAS)

AF:

0.100

AC:

8549

AN:

85432

European-Finnish (FIN)

AF:

0.127

AC:

6756

AN:

53384

Middle Eastern (MID)

AF:

0.0594

AC:

342

AN:

5758

European-Non Finnish (NFE)

AF:

0.0944

AC:

104783

AN:

1109446

Other (OTH)

AF:

0.0962

AC:

5793

AN:

60194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

5704

11407

17111

22814

28518

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3870

7740

11610

15480

19350

<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:

0.0923

AC:

14040

AN:

152160

Hom.:

814

Cov.:

AF XY:

0.0957

AC XY:

7115

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0306

AC:

1270

AN:

41548

American (AMR)

AF:

0.187

AC:

2858

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.0772

AC:

268

AN:

3470

East Asian (EAS)

AF:

0.175

AC:

902

AN:

5166

South Asian (SAS)

AF:

0.107

AC:

514

AN:

4822

European-Finnish (FIN)

AF:

0.128

AC:

1353

AN:

10584

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0961

AC:

6534

AN:

68006

Other (OTH)

AF:

0.0886

AC:

186

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

625

1250

1876

2501

3126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<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:

0.0926

Hom.:

2367

Bravo

AF:

0.0943

Asia WGS

AF:

0.148

AC:

515

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.6

(source)

DANN

Benign

0.86

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over