chr4-184117800-C-T

Position:

• chr4-184117800-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153343.4(ENPP6):​c.634G>A​(p.Ala212Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ENPP6 NM_153343.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20

Genes affected

ENPP6 (HGNC:23409): (ectonucleotide pyrophosphatase/phosphodiesterase 6) Enables glycerophosphocholine cholinephosphodiesterase activity. Involved in choline metabolic process and lipid metabolic process. Located in extracellular region and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3230561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP6	NM_153343.4	c.634G>A	p.Ala212Thr	missense_variant	4/8	ENST00000296741.7	NP_699174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENPP6	ENST00000296741.7	c.634G>A	p.Ala212Thr	missense_variant	4/8	1	NM_153343.4	ENSP00000296741	P1
ENPP6	ENST00000512353.1	c.370G>A	p.Ala124Thr	missense_variant	5/6	3		ENSP00000423497
ENPP6	ENST00000510054.1	n.22G>A		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Sep 27, 2021

The c.634G>A (p.A212T) alteration is located in exon 4 (coding exon 4) of the ENPP6 gene. This alteration results from a G to A substitution at nucleotide position 634, causing the alanine (A) at amino acid position 212 to be replaced by a threonine (T). 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	Benign	0.11
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	0.98	D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.77	N;N
REVEL	Benign	0.17
Sift	Benign	0.23	T;T
Sift4G	Benign	0.52	T;.
Polyphen		0.58	P;.
Vest4		0.18
MutPred		0.50		Loss of ubiquitination at K211 (P = 0.0834);.;
MVP		0.83
MPC		0.44
ClinPred		0.82	D
GERP RS		5.2
Varity_R		0.078
gMVP		0.63

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: chr4-185038953;