rs58085394

chr18-706558-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017512.7(ENOSF1):c.105G>A(p.Ser35=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ENOSF1	NM_017512.7	c.105G>A	p.Ser35=	synonymous_variant	2/16	ENST00000647584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOSF1	ENST00000647584.2	c.105G>A	p.Ser35=	synonymous_variant	2/16		NM_017512.7	P1
	ENST00000580007.1	n.36C>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16192 AN: 151756 Hom.: 1087 Cov.: 31

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

GnomAD3 exomes AF: 0.125 AC: 31442 AN: 251422 Hom.: 2433 AF XY: 0.124 AC XY: 16914 AN XY: 135888

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 SAS exome AF: 0.0483

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.: 31 AF XY: 0.132 AC XY: 95829 AN XY: 726704

Gnomad4 AFR exome AF: 0.0249

Gnomad4 AMR exome AF: 0.0904

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.0486

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.107 AC: 16182 AN: 151872 Hom.: 1085 Cov.: 31 AF XY: 0.106 AC XY: 7846 AN XY: 74182

Gnomad4 AFR AF: 0.0297

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.0520

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.118

Alfa AF: 0.131 Hom.: 744

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
Dann	Benign	0.81
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

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

Other links and lift over

dbSNP: rs58085394; hg19: chr18-706558; COSMIC: COSV51891452;