18-673995-T-G

Variant names:

• chr18-673995-T-G
• rs1059384
• ENST00000581475.5:n.*1029A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000581475.5(ENOSF1):​n.*1029A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 207,496 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: ENOSF1 ENST00000581475.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 13 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENOSF1	NM_017512.7	c.*310A>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000647584.2	NP_059982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584.2	c.*310A>C		3_prime_UTR_variant	Exon 16 of 16		NM_017512.7	ENSP00000497230.2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151836 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000180 AC: 1 AN: 55660 Hom.: 0 Cov.: 0 AF XY: 0.0000352 AC XY: 1 AN XY: 28392

African (AFR) AF: 0.00 AC: 0 AN: 1740

American (AMR) AF: 0.00 AC: 0 AN: 1990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1984

East Asian (EAS) AF: 0.00 AC: 0 AN: 3012

South Asian (SAS) AF: 0.00 AC: 0 AN: 3396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 36802

Other (OTH) AF: 0.000264 AC: 1 AN: 3792

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151836 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74146

African (AFR) AF: 0.0000242 AC: 1 AN: 41274

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 9542

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		0.13

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: rs1059384; hg19: chr18-673995;