chr18-691266-A-C

Variant names:

• chr18-691266-A-C
• rs2612086
• NM_017512.7:c.434T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001354067.2(ENOSF1):​c.578T>G​(p.Met193Arg) variant causes a missense 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. 16/21 in silico tools predict 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)
• Consequence: ENOSF1 NM_001354067.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10867289).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354067.2. 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.434T>G	p.Met145Arg	missense	Exon 6 of 16	NP_059982.2
	ENOSF1	NM_001354067.2		c.578T>G	p.Met193Arg	missense	Exon 6 of 16	NP_001340996.1
	ENOSF1	NM_202758.5		c.578T>G	p.Met193Arg	missense	Exon 6 of 15	NP_974487.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOSF1	ENST00000647584.2	MANE Select	c.434T>G	p.Met145Arg	missense	Exon 6 of 16	ENSP00000497230.2
	ENOSF1	ENST00000383578.7	TSL:1	c.188T>G	p.Met63Arg	missense	Exon 5 of 16	ENSP00000373072.3
	ENOSF1	ENST00000581475.5	TSL:1	n.424-521T>G		intron	N/A	ENSP00000464614.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.18
DANN	Benign	0.92
DEOGEN2	Benign	0.043	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.12	N
PhyloP100		-0.022
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.033
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.047	D
Polyphen		0.0	B
Vest4		0.11
MutPred		0.59		Loss of stability (P = 0.0777)
MVP		0.014
MPC		0.014
ClinPred		0.26	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15

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: rs2612086; hg19: chr18-691266;