Genetic Variant ENOSF1:p.Ser35Ser (chr18-706558-C-T) – 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.105G>A(p.Ser35Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,612,488 control chromosomes in the GnomAD database, including 15,140 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 0.11 ( 1085 hom., cov: 31)

Exomes 𝑓: 0.13 ( 14055 hom. )

Consequence

ENOSF1
NM_017512.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.17

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:

ENSG00000265490 (HGNC:):

ENSG00000265490 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=-0.62).

BP7

Synonymous conserved (PhyloP=-1.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENOSF1	NM_017512.7 link	c.105G>A	p.Ser35Ser	synonymous_variant	Exon 2 of 16	ENST00000647584.2	NP_059982.2	Q7L5Y1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584.2 link	c.105G>A	p.Ser35Ser	synonymous_variant	Exon 2 of 16		NM_017512.7	ENSP00000497230.2		Q7L5Y1-1

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16192

AN:

151756

Hom.:

1087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0297

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.0956

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.0517

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.119

GnomAD2 exomes

AF:

0.125

AC:

31442

AN:

251422

AF XY:

0.124

show subpopulations

Gnomad AFR exome

AF:

0.0250

Gnomad AMR exome

AF:

0.0905

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.134

AC:

195193

AN:

1460616

Hom.:

14055

Cov.:

AF XY:

0.132

AC XY:

95829

AN XY:

726704

show subpopulations

African (AFR)

AF:

0.0249

AC:

833

AN:

33472

American (AMR)

AF:

0.0904

AC:

4040

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

4074

AN:

26112

East Asian (EAS)

AF:

0.206

AC:

8172

AN:

39674

South Asian (SAS)

AF:

0.0486

AC:

4194

AN:

86228

European-Finnish (FIN)

AF:

0.138

AC:

7358

AN:

53404

Middle Eastern (MID)

AF:

0.128

AC:

737

AN:

5766

European-Non Finnish (NFE)

AF:

0.142

AC:

157938

AN:

1110896

Other (OTH)

AF:

0.130

AC:

7847

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

7872

15744

23617

31489

39361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.107

AC:

16182

AN:

151872

Hom.:

1085

Cov.:

AF XY:

0.106

AC XY:

7846

AN XY:

74182

show subpopulations

African (AFR)

AF:

0.0297

AC:

1230

AN:

41442

American (AMR)

AF:

0.0954

AC:

1453

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

493

AN:

3468

East Asian (EAS)

AF:

0.235

AC:

1208

AN:

5150

South Asian (SAS)

AF:

0.0520

AC:

250

AN:

4810

European-Finnish (FIN)

AF:

0.132

AC:

1390

AN:

10510

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9674

AN:

67952

Other (OTH)

AF:

0.118

AC:

249

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

714

1428

2142

2856

3570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.131

Hom.:

1002

Bravo

AF:

0.103

Asia WGS

AF:

0.125

AC:

435

AN:

3478

EpiCase

AF:

0.145

EpiControl

AF:

0.146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.8

(source)

DANN

Benign

0.81

PhyloP100

-1.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Mutation Taster

=300/0

polymorphism (auto)

(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

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chr18-706558-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over