6-46139575-G-C

Variant names:

• chr6-46139575-G-C
• rs11752816
• NM_014936.5:c.-9G>C

Variant summary

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

The NM_014936.5(ENPP4):​c.-9G>C variant causes a 5 prime UTR premature start codon gain 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: 31)
• Consequence: ENPP4 NM_014936.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• Publications: 10 publications found

Genes affected

ENPP4 (HGNC:3359): (ectonucleotide pyrophosphatase/phosphodiesterase 4) Enables bis(5'-adenosyl)-triphosphatase activity. Involved in positive regulation of blood coagulation and purine ribonucleoside catabolic process. Located in extracellular exosome and membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014936.5. 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
	ENPP4	NM_014936.5	MANE Select	c.-9G>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	NP_055751.1	Q9Y6X5
	ENPP4	NM_014936.5	MANE Select	c.-9G>C		5_prime_UTR	Exon 2 of 4	NP_055751.1	Q9Y6X5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP4	ENST00000321037.5	TSL:1 MANE Select	c.-9G>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000318066.3	Q9Y6X5
	ENPP4	ENST00000321037.5	TSL:1 MANE Select	c.-9G>C		5_prime_UTR	Exon 2 of 4	ENSP00000318066.3	Q9Y6X5
	ENPP4	ENST00000962953.1		c.-9G>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000633012.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 16

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.27
DANN	Benign	0.76
PhyloP100		-0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11752816; hg19: chr6-46107312;