9-94318479-G-A

Variant names:

• chr9-94318479-G-A
• NM_017561.2:c.2257C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017561.2(NUTM2F):​c.2257C>T​(p.His753Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 10)
  • Exomes 𝑓: 0.0000054 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2F NM_017561.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.166

Genes affected

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

LOC105376154 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14866686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM2F	NM_017561.2	c.2257C>T	p.His753Tyr	missense_variant	Exon 7 of 7	ENST00000253262.9	NP_060031.1
LOC105376154	XR_001746842.3	n.607+3469G>A		intron_variant	Intron 2 of 2
LOC105376154	XR_930132.4	n.190+3469G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUTM2F	ENST00000253262.9	c.2257C>T	p.His753Tyr	missense_variant	Exon 7 of 7	1	NM_017561.2	ENSP00000253262.4

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000540 AC: 4 AN: 741384 Hom.: 0 Cov.: 10 AF XY: 0.00000262 AC XY: 1 AN XY: 382090

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: 0.00000800

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2257C>T (p.H753Y) 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 2257, causing the histidine (H) at amino acid position 753 to be replaced by a tyrosine (Y). 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	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.4
DANN	Benign	0.93
DEOGEN2	Benign	0.0088	T;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.035
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.61	P;.
Vest4		0.17
MutPred		0.17		Gain of phosphorylation at H753 (P = 0.0677);.;
MVP		0.014
ClinPred		0.21	T
GERP RS		1.2
Varity_R		0.13
gMVP		0.019

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.

Other links and lift over

hg19: chr9-97080761;