Variant 5-138115749-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003551.3(NME5):c.571T>C(p.Trp191Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000839 in 1,431,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

NME5
NM_003551.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.92

Variant links:

Genes affected

NME5 (HGNC:7853): (NME/NM23 family member 5) Predicted to enable nucleoside diphosphate kinase activity. Predicted to be involved in negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway and spermatid development. Predicted to act upstream of or within cilium assembly; epithelial cilium movement involved in extracellular fluid movement; and ventricular system development. Predicted to be located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

NME5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.891

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NME5	NM_003551.3 linkuse as main transcript	c.571T>C	p.Trp191Arg	missense_variant	6/6	ENST00000265191.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NME5	ENST00000265191.4 linkuse as main transcript	c.571T>C	p.Trp191Arg	missense_variant	6/6	1	NM_003551.3	P1
NME5	ENST00000506657.1 linkuse as main transcript	n.300T>C		non_coding_transcript_exon_variant	3/3	2
NME5	ENST00000514481.1 linkuse as main transcript	n.156T>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000839

AC:

AN:

1431096

Hom.:

Cov.:

AF XY:

0.00000843

AC XY:

AN XY:

711798

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:

0.00000998

Gnomad4 OTH exome

AF:

0.0000170

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

Dec 21, 2023

The c.571T>C (p.W191R) alteration is located in exon 6 (coding exon 5) of the NME5 gene. This alteration results from a T to C substitution at nucleotide position 571, causing the tryptophan (W) at amino acid position 191 to be replaced by an arginine (R). 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

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.053

MetaRNN

Pathogenic

0.89

MetaSVM

Uncertain

0.051

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-12

REVEL

Uncertain

0.64

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.83

MutPred

0.70

Gain of disorder (P = 0.0123);

MVP

0.81

MPC

1.1

ClinPred

1.0

GERP RS

5.4

Varity_R

0.91

gMVP

0.92

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over