chr6-46139883-A-T

Position:

• chr6-46139883-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014936.5(ENPP4):​c.300A>T​(p.Lys100Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENPP4 NM_014936.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP4	NM_014936.5	c.300A>T	p.Lys100Asn	missense_variant	2/4	ENST00000321037.5	NP_055751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENPP4	ENST00000321037.5	c.300A>T	p.Lys100Asn	missense_variant	2/4	1	NM_014936.5	ENSP00000318066	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.300A>T (p.K100N) alteration is located in exon 2 (coding exon 1) of the ENPP4 gene. This alteration results from a A to T substitution at nucleotide position 300, causing the lysine (K) at amino acid position 100 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.097
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Pathogenic	3.1	M
MutationTaster	Benign	0.67	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.048	D
Polyphen		0.96	D
Vest4		0.43
MutPred		0.56		Loss of methylation at K100 (P = 0.0047);
MVP		0.82
MPC		0.16
ClinPred		0.96	D
GERP RS		2.4
Varity_R		0.87
gMVP		0.96

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-46107620;