chr18-674320-A-G

Variant names:

• chr18-674320-A-G
• rs3744962
• NM_017512.7:c.1317T>C

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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 29 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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017512.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOSF1	NM_017512.7	MANE Select	c.1317T>C	p.Pro439Pro	synonymous	Exon 16 of 16	NP_059982.2
	ENOSF1	NM_001354067.2		c.1461T>C	p.Pro487Pro	synonymous	Exon 16 of 16	NP_001340996.1
	ENOSF1	NM_202758.5		c.1419T>C	p.Pro473Pro	synonymous	Exon 15 of 15	NP_974487.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOSF1	ENST00000647584.2	MANE Select	c.1317T>C	p.Pro439Pro	synonymous	Exon 16 of 16	ENSP00000497230.2
	ENOSF1	ENST00000383578.7	TSL:1	c.1071T>C	p.Pro357Pro	synonymous	Exon 15 of 16	ENSP00000373072.3
	ENOSF1	ENST00000581475.5	TSL:1	n.*704T>C		non_coding_transcript_exon	Exon 14 of 14	ENSP00000464614.1

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

GnomAD2 exomes AF: 0.116 AC: 28621 AN: 247214 AF XY: 0.111

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

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

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

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: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0961 AC: 6534 AN: 68006

Other (OTH) AF: 0.0886 AC: 186 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.6
DANN	Benign	0.86
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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