ENST00000647584:c.*910C>T

Variant names:

• chr18-673395-G-A
• rs16948421
• NM_017512.7:c.*910C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000647584.2(ENOSF1):​c.*910C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 227,284 control chromosomes in the GnomAD database, including 434 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 0.040 (414 hom., cov: 33)
  • Exomes 𝑓: 0.0072 (20 hom.)
• Consequence: ENOSF1 ENST00000647584.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000647584.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOSF1	NM_017512.7	MANE Select	c.*910C>T		3_prime_UTR	Exon 16 of 16	NP_059982.2
	TYMS	NM_001071.4	MANE Select	c.*398G>A		3_prime_UTR	Exon 7 of 7	NP_001062.1	Q53Y97
	ENOSF1	NM_001354067.2		c.*910C>T		3_prime_UTR	Exon 16 of 16	NP_001340996.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOSF1	ENST00000647584.2	MANE Select	c.*910C>T		3_prime_UTR	Exon 16 of 16	ENSP00000497230.2	Q7L5Y1-1
	TYMS	ENST00000323274.15	TSL:1 MANE Select	c.*398G>A		3_prime_UTR	Exon 7 of 7	ENSP00000315644.10	P04818-1
	TYMS	ENST00000323224.7	TSL:1	c.*398G>A		3_prime_UTR	Exon 6 of 6	ENSP00000314727.7	P04818-2

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6125 AN: 152092 Hom.: 414 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0292

GnomAD4 exome AF: 0.00715 AC: 537 AN: 75074 Hom.: 20 Cov.: 0 AF XY: 0.00614 AC XY: 215 AN XY: 35010

African (AFR) AF: 0.123 AC: 401 AN: 3266

American (AMR) AF: 0.00976 AC: 35 AN: 3586

Ashkenazi Jewish (ASJ) AF: 0.00201 AC: 9 AN: 4488

East Asian (EAS) AF: 0.00 AC: 0 AN: 10124

South Asian (SAS) AF: 0.00 AC: 0 AN: 1166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 138

Middle Eastern (MID) AF: 0.00239 AC: 1 AN: 418

European-Non Finnish (NFE) AF: 0.000414 AC: 19 AN: 45904

Other (OTH) AF: 0.0120 AC: 72 AN: 5984

GnomAD4 genome AF: 0.0404 AC: 6142 AN: 152210 Hom.: 414 Cov.: 33 AF XY: 0.0392 AC XY: 2921 AN XY: 74430

African (AFR) AF: 0.141 AC: 5834 AN: 41486

American (AMR) AF: 0.0133 AC: 203 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68020

Other (OTH) AF: 0.0289 AC: 61 AN: 2114

Alfa AF: 0.0160 Hom.: 373

Bravo AF: 0.0456

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.50
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs16948421; hg19: chr18-673395;