rs58085394

Variant names:

• chr18-706558-C-T
• rs58085394
• NM_017512.7:c.105G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 8 publications found

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]

ENSG00000265490 (HGNC:):

ACMG classification

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	c.105G>A	p.Ser35Ser	synonymous_variant	Exon 2 of 16	ENST00000647584.2	NP_059982.2

Ensembl

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

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

GnomAD2 exomes AF: 0.125 AC: 31442 AN: 251422 AF XY: 0.124

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

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

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

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: 66 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9674 AN: 67952

Other (OTH) AF: 0.118 AC: 249 AN: 2108

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
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)

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

Other links and lift over

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