Genetic Variant NME6:p.Leu94Pro (chr3-48295188-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001308426.2(NME6):c.281T>C(p.Leu94Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

NME6
NM_001308426.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

Publications

1 publications found

Variant links:

Genes affected

NME6 (HGNC:20567): (NME/NM23 nucleoside diphosphate kinase 6) Nucleoside diphosphate (NDP) kinases (EC 2.7.4.6), such as NME6, are ubiquitous enzymes that catalyze transfer of gamma-phosphates, via a phosphohistidine intermediate, between nucleoside and dioxynucleoside tri- and diphosphates (Mehus et al., 1999 [PubMed 10453732]).[supplied by OMIM, Jul 2010]

NME6 links:

ZNF589 (HGNC:16747): (zinc finger protein 589) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF589 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ZNF589 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40451765).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308426.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NME6	NM_001308426.2	MANE Select	c.281T>C	p.Leu94Pro	missense	Exon 5 of 6	NP_001295355.1	O75414-1
NME6	NM_001438659.1		c.281T>C	p.Leu94Pro	missense	Exon 5 of 6	NP_001425588.1
NME6	NM_001438660.1		c.281T>C	p.Leu94Pro	missense	Exon 5 of 6	NP_001425589.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NME6	ENST00000442597.6	TSL:1 MANE Select	c.281T>C	p.Leu94Pro	missense	Exon 5 of 6	ENSP00000406642.1	O75414-1
NME6	ENST00000421967.5	TSL:1	c.305T>C	p.Leu102Pro	missense	Exon 5 of 6	ENSP00000416658.1	A0A0C4DG91
NME6	ENST00000426689.6	TSL:1	c.281T>C	p.Leu94Pro	missense	Exon 4 of 5	ENSP00000440286.1	O75414-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000354

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.061

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.011

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.89

PhyloP100

2.3

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.6

REVEL

Benign

0.17

Sift

Benign

0.20

Sift4G

Benign

0.36

Polyphen

0.16

Vest4

0.80

MVP

0.72

MPC

0.69

ClinPred

0.96

GERP RS

4.9

Varity_R

0.88

gMVP

0.92

Mutation Taster

=51/49

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over