Genetic Variant NUTM2F:p.Arg566Cys (chr9-94319040-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_017561.2(NUTM2F):c.1696C>T(p.Arg566Cys) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000085 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000026 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NUTM2F
NM_017561.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.11

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04191771).

BP6

Variant 9-94319040-G-A is Benign according to our data. Variant chr9-94319040-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3408953.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM2F	NM_017561.2 link	c.1696C>T	p.Arg566Cys	missense_variant	Exon 7 of 7	ENST00000253262.9	NP_060031.1	A1L443
LOC105376154	XR_001746842.3 link	n.607+4030G>A		intron_variant	Intron 2 of 2
LOC105376154	XR_930132.4 link	n.190+4030G>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.1696C>T	p.Arg566Cys	missense_variant	Exon 7 of 7	1	NM_017561.2	ENSP00000253262.4		A1L443

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

117950

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000330

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000299

AC:

AN:

234088

Hom.:

AF XY:

0.0000314

AC XY:

AN XY:

127342

show subpopulations

Gnomad AFR exome

AF:

0.000218

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000698

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000259

AC:

AN:

1429700

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

711624

show subpopulations

Gnomad4 AFR exome

AF:

0.0000911

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000357

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000248

Gnomad4 OTH exome

AF:

0.0000675

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000848

AC:

AN:

117950

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

56098

show subpopulations

Gnomad4 AFR

AF:

0.0000330

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:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000250

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 09, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.47

DANN

Benign

0.50

DEOGEN2

Benign

0.00075

T;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.00065

LIST_S2

Benign

0.27

T;T

M_CAP

Benign

0.00096

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.26

N;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.30

N;N

REVEL

Benign

0.0060

Sift

Benign

0.24

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.0010

B;.

Vest4

0.066

MutPred

0.26

Loss of MoRF binding (P = 0.0162);.;

MVP

0.014

ClinPred

0.013

GERP RS

-2.9

Varity_R

0.051

gMVP

0.060

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