Genetic Variant NUTM2F:p.Leu501Pro (chr9-94319234-A-G) – 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.1502T>C(p.Leu501Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 2 hom., cov: 14)

Exomes 𝑓: 0.0016 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

NUTM2F
NM_017561.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.887

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=0.042035043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM2F	NM_017561.2 link	c.1502T>C	p.Leu501Pro	missense_variant	Exon 7 of 7	ENST00000253262.9	NP_060031.1	A1L443
LOC105376154	XR_001746842.3 link	n.607+4224A>G		intron_variant	Intron 2 of 2
LOC105376154	XR_930132.4 link	n.190+4224A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUTM2F	ENST00000253262.9 link	c.1502T>C	p.Leu501Pro	missense_variant	Exon 7 of 7	1	NM_017561.2	ENSP00000253262.4		A1L443

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

163

AN:

116760

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000477

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00302

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:

0.00207

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000921

AC:

AN:

65120

Hom.:

AF XY:

0.000813

AC XY:

AN XY:

33190

show subpopulations

Gnomad AFR exome

AF:

0.000184

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00179

Gnomad OTH exome

AF:

0.000958

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00163

AC:

1391

AN:

852514

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

686

AN XY:

428660

show subpopulations

Gnomad4 AFR exome

AF:

0.000203

Gnomad4 AMR exome

AF:

0.000934

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000180

Gnomad4 FIN exome

AF:

0.000125

Gnomad4 NFE exome

AF:

0.00207

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00139

AC:

163

AN:

116862

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

AN XY:

54848

show subpopulations

Gnomad4 AFR

AF:

0.000475

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00207

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000256

Hom.:

Bravo

AF:

0.00155

ExAC

AF:

0.000234

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1502T>C (p.L501P) alteration is located in exon 7 (coding exon 7) of the NUTM2F gene. This alteration results from a T to C substitution at nucleotide position 1502, causing the leucine (L) at amino acid position 501 to be replaced by a proline (P). 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

0.33

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.092

T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

2.9

M;.

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Benign

0.096

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.029

D;D

Polyphen

1.0

D;.

Vest4

0.52

MVP

0.081

ClinPred

0.099

GERP RS

1.4

Varity_R

0.40

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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