rs4479748

Variant names:

• chr4-184091245-T-A
• rs4479748
• NM_153343.4:c.1255A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-184091245-T-A
• chr4-184091245-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_153343.4(ENPP6):​c.1255A>T​(p.Ser419Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,445,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ENPP6 NM_153343.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• Publications: 0 publications found

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]

LOC124900826 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM1: In a lipid_moiety_binding_region GPI-anchor amidated serine (size 0) in uniprot entity ENPP6_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18995667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENPP6	NM_153343.4	c.1255A>T	p.Ser419Cys	missense_variant	Exon 8 of 8	ENST00000296741.7	NP_699174.1
LOC124900826	XR_007058415.1	n.2028-852T>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP6	ENST00000296741.7	c.1255A>T	p.Ser419Cys	missense_variant	Exon 8 of 8	1	NM_153343.4	ENSP00000296741.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1445328 Hom.: 0 Cov.: 57 AF XY: 0.00000139 AC XY: 1 AN XY: 717240

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.00 AC: 0 AN: 43816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24698

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 82128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1103904

Other (OTH) AF: 0.00 AC: 0 AN: 59788

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	5.1
DANN	Benign	0.80
DEOGEN2	Benign	0.052	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.23	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.43
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.31
Sift	Benign	0.27	T
Sift4G	Uncertain	0.027	D
Polyphen		0.56	P
Vest4		0.22
MutPred		0.50		Loss of glycosylation at S419 (P = 0.0037);
MVP		0.59
MPC		0.20
ClinPred		0.45	T
GERP RS		-5.0
Varity_R		0.057
gMVP		0.38
Mutation Taster		=98/2	polymorphism

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: rs4479748; hg19: chr4-185012398;