rs1428350818

Variant names:

• chr9-94318787-C-T
• rs1428350818
• NM_017561.2:c.1949G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017561.2(NUTM2F):​c.1949G>A​(p.Arg650Lys) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000050 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2F NM_017561.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.33

Genes affected

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

LOC105376154 (HGNC:):

ACMG classification

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=0.07774833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM2F	NM_017561.2	c.1949G>A	p.Arg650Lys	missense_variant	Exon 7 of 7	ENST00000253262.9	NP_060031.1
LOC105376154	XR_001746842.3	n.607+3777C>T		intron_variant	Intron 2 of 2
LOC105376154	XR_930132.4	n.190+3777C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUTM2F	ENST00000253262.9	c.1949G>A	p.Arg650Lys	missense_variant	Exon 7 of 7	1	NM_017561.2	ENSP00000253262.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.0000225 AC: 3 AN: 133578 Hom.: 0 AF XY: 0.0000285 AC XY: 2 AN XY: 70068

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000905

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: 0.00

Gnomad OTH exome AF: 0.000266

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000500 AC: 7 AN: 1399130 Hom.: 0 Cov.: 32 AF XY: 0.00000434 AC XY: 3 AN XY: 690824

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000139

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: 0.00000186

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1949G>A (p.R650K) alteration is located in exon 7 (coding exon 7) of the NUTM2F gene. This alteration results from a G to A substitution at nucleotide position 1949, causing the arginine (R) at amino acid position 650 to be replaced by a lysine (K). 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	0.15
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.34
DANN	Benign	0.59
DEOGEN2	Benign	0.0045	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.014
Sift	Benign	0.21	T;T
Sift4G	Benign	0.78	T;T
Polyphen		0.054	B;.
Vest4		0.088
MutPred		0.23		Gain of methylation at R650 (P = 0.0409);.;
MVP		0.014
ClinPred		0.18	T
GERP RS		0.30
Varity_R		0.046
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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

Other links and lift over

dbSNP: rs1428350818; hg19: chr9-97081069;