NM_017512.7:c.*1219T>A

Variant names:

• chr18-673086-A-T
• rs2790
• NM_017512.7:c.*1219T>A

Variant summary

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

The NM_017512.7(ENOSF1):​c.*1219T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENOSF1 NM_017512.7 3_prime_UTR
• Scores: Splicing: ADA: 0.00004852
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.707
• Publications: 56 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]

TYMS (HGNC:12441): (thymidylate synthetase) Thymidylate synthase catalyzes the methylation of deoxyuridylate to deoxythymidylate using, 10-methylenetetrahydrofolate (methylene-THF) as a cofactor. This function maintains the dTMP (thymidine-5-prime monophosphate) pool critical for DNA replication and repair. The enzyme has been of interest as a target for cancer chemotherapeutic agents. It is considered to be the primary site of action for 5-fluorouracil, 5-fluoro-2-prime-deoxyuridine, and some folate analogs. Expression of this gene and that of a naturally occurring antisense transcript, mitochondrial enolase superfamily member 1 (GeneID:55556), vary inversely when cell-growth progresses from late-log to plateau phase. Polymorphisms in this gene may be associated with etiology of neoplasia, including breast cancer, and response to chemotherapy. [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=-0.83).

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.*1219T>A		3_prime_UTR	Exon 16 of 16	NP_059982.2
	TYMS	NM_001071.4	MANE Select	c.*89A>T		3_prime_UTR	Exon 7 of 7	NP_001062.1
	ENOSF1	NM_001354067.2		c.*1219T>A		3_prime_UTR	Exon 16 of 16	NP_001340996.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOSF1	ENST00000647584.2	MANE Select	c.*1219T>A		3_prime_UTR	Exon 16 of 16	ENSP00000497230.2
	TYMS	ENST00000323274.15	TSL:1 MANE Select	c.*89A>T		3_prime_UTR	Exon 7 of 7	ENSP00000315644.10
	TYMS	ENST00000323224.7	TSL:1	c.*89A>T		3_prime_UTR	Exon 6 of 6	ENSP00000314727.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1227320 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 597854

African (AFR) AF: 0.00 AC: 0 AN: 28458

American (AMR) AF: 0.00 AC: 0 AN: 28608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18224

East Asian (EAS) AF: 0.00 AC: 0 AN: 37884

South Asian (SAS) AF: 0.00 AC: 0 AN: 46238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4868

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 969952

Other (OTH) AF: 0.00 AC: 0 AN: 49580

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.63
PhyloP100		0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000049
dbscSNV1_RF	Benign	0.010
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: rs2790; hg19: chr18-673086;