Genetic Variant NUTM2F:p.Arg752Trp (chr9-94318482-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017561.2(NUTM2F):c.2254C>T(p.Arg752Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 10)

Exomes 𝑓: 0.000033 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NUTM2F
NM_017561.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.815

Variant links:

Genes affected

NUTM2F (HGNC:23450): (NUT family member 2F)

NUTM2F links:

LOC105376154 (HGNC:):

LOC105376154 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063792765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM2F	NM_017561.2 link	c.2254C>T	p.Arg752Trp	missense_variant	Exon 7 of 7	ENST00000253262.9	NP_060031.1	A1L443
LOC105376154	XR_001746842.3 link	n.607+3472G>A		intron_variant	Intron 2 of 2
LOC105376154	XR_930132.4 link	n.190+3472G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUTM2F	ENST00000253262.9 link	c.2254C>T	p.Arg752Trp	missense_variant	Exon 7 of 7	1	NM_017561.2	ENSP00000253262.4		A1L443

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

77516

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000467

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000289

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000824

AC:

AN:

72788

Hom.:

AF XY:

0.0000535

AC XY:

AN XY:

37374

show subpopulations

Gnomad AFR exome

AF:

0.000847

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000116

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000328

AC:

AN:

762444

Hom.:

Cov.:

AF XY:

0.0000204

AC XY:

AN XY:

392538

show subpopulations

Gnomad4 AFR exome

AF:

0.000725

Gnomad4 AMR exome

AF:

0.0000343

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000299

Gnomad4 SAS exome

AF:

0.0000333

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000580

Gnomad4 OTH exome

AF:

0.0000542

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000155

AC:

AN:

77644

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

AN XY:

35850

show subpopulations

Gnomad4 AFR

AF:

0.000465

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000289

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000260

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2254C>T (p.R752W) alteration is located in exon 7 (coding exon 7) of the NUTM2F gene. This alteration results from a C to T substitution at nucleotide position 2254, causing the arginine (R) at amino acid position 752 to be replaced by a tryptophan (W). 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

0.065

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.0022

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.0064

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.72

N;N

REVEL

Benign

0.012

Sift

Benign

0.10

T;D

Sift4G

Benign

0.099

T;T

Polyphen

0.022

B;.

Vest4

0.18

MutPred

0.31

Loss of solvent accessibility (P = 0.0199);.;

MVP

0.030

ClinPred

0.0099

GERP RS

-1.2

Varity_R

0.041

gMVP

0.036

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