rs3744962

chr18-674320-A-G

Variant summary

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

The NM_017512.7(ENOSF1):c.1317T>C(p.Pro439=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ENOSF1	NM_017512.7	c.1317T>C	p.Pro439=	synonymous_variant	16/16	ENST00000647584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOSF1	ENST00000647584.2	c.1317T>C	p.Pro439=	synonymous_variant	16/16		NM_017512.7	P1

Frequencies

GnomAD3 genomes AF: 0.0923 AC: 14029 AN: 152042 Hom.: 815 Cov.: 32

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

GnomAD3 exomes AF: 0.116 AC: 28621 AN: 247214 Hom.: 2104 AF XY: 0.111 AC XY: 14882 AN XY: 133726

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 SAS exome AF: 0.0964

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.: 30 AF XY: 0.100 AC XY: 72734 AN XY: 724750

Gnomad4 AFR exome AF: 0.0293

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.0849

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.0944

Gnomad4 OTH exome AF: 0.0962

GnomAD4 genome AF: 0.0923 AC: 14040 AN: 152160 Hom.: 814 Cov.: 32 AF XY: 0.0957 AC XY: 7115 AN XY: 74366

Gnomad4 AFR AF: 0.0306

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0961

Gnomad4 OTH AF: 0.0886

Alfa AF: 0.0936 Hom.: 1619

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
Dann	Benign	0.86

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

LitVar

Other links and lift over

dbSNP: rs3744962; hg19: chr18-674320; COSMIC: COSV51892835; COSMIC: COSV51892835;