Genetic Variant NUTM2G:p.Ser205Arg (chr9-96932320-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001170741.3(NUTM2G):c.615T>G(p.Ser205Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NUTM2G
NM_001170741.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.74

Variant links:

Genes affected

NUTM2G (HGNC:23449): (NUT family member 2G)

NUTM2G links:

ZNF782 (HGNC:33110): (zinc finger protein 782) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF782 links:

MFSD14CP (HGNC:):

MFSD14CP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19816226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM2G	NM_001170741.3 link	c.615T>G	p.Ser205Arg	missense_variant	Exon 2 of 7	ENST00000372322.4	NP_001164212.1	Q5VZR2-1
NUTM2G	NM_001045477.4 link	c.615T>G	p.Ser205Arg	missense_variant	Exon 2 of 7		NP_001038942.1	Q5VZR2-2
ZNF782	XM_047422874.1 link	c.-439+1464A>C		intron_variant	Intron 1 of 3		XP_047278830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUTM2G	ENST00000372322.4 link	c.615T>G	p.Ser205Arg	missense_variant	Exon 2 of 7	5	NM_001170741.3	ENSP00000361397.3		Q5VZR2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1460382

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726454

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

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

Dec 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.615T>G (p.S205R) alteration is located in exon 2 (coding exon 2) of the NUTM2G gene. This alteration results from a T to G substitution at nucleotide position 615, causing the serine (S) at amino acid position 205 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

0.81

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.072

.;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.0083

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0021

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

2.9

M;M

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0090

D;D

Sift4G

Benign

0.12

T;D

Polyphen

1.0

D;.

Vest4

0.26

MutPred

0.16

Loss of ubiquitination at K202 (P = 0.0149);Loss of ubiquitination at K202 (P = 0.0149);

MVP

0.030

ClinPred

0.98

GERP RS

-2.1

Varity_R

0.39

gMVP

0.21

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