Variant chr16-397286-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005009.3(NME4):c.64C>T(p.Pro22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 912,818 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 26)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

NME4
NM_005009.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00900

Variant links:

Genes affected

NME4 (HGNC:7852): (NME/NM23 nucleoside diphosphate kinase 4) The nucleoside diphosphate (NDP) kinases (EC 2.7.4.6) are ubiquitous enzymes that catalyze transfer of gamma-phosphates, via a phosphohistidine intermediate, between nucleoside and dioxynucleoside tri- and diphosphates. The enzymes are products of the nm23 gene family, which includes NME4 (Milon et al., 1997 [PubMed 9099850]).[supplied by OMIM, May 2008]

NME4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.116834015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NME4	NM_005009.3 linkuse as main transcript	c.64C>T	p.Pro22Ser	missense_variant	1/5	ENST00000219479.7	NP_005000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NME4	ENST00000219479.7 linkuse as main transcript	c.64C>T	p.Pro22Ser	missense_variant	1/5	1	NM_005009.3	ENSP00000219479	P2	O00746-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000657

AC:

AN:

912818

Hom.:

Cov.:

AF XY:

0.00000937

AC XY:

AN XY:

426962

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000737

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.64C>T (p.P22S) alteration is located in exon 1 (coding exon 1) of the NME4 gene. This alteration results from a C to T substitution at nucleotide position 64, causing the proline (P) at amino acid position 22 to be replaced by a serine (S). 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

0.080

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.67

T;T;T

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.37

.;N;N

REVEL

Benign

0.041

Sift

Benign

0.18

.;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.19

.;.;B

Vest4

0.24

MutPred

0.18

Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);

MVP

0.67

MPC

0.13

ClinPred

0.13

GERP RS

0.018

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

Varity_R

0.029

gMVP

0.32

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over