9-94318896-G-T

Variant names:

• chr9-94318896-G-T
• rs763606215
• NM_017561.2:c.1840C>A

Variant summary

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

The NM_017561.2(NUTM2F):​c.1840C>A​(p.Leu614Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2F NM_017561.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.331

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=0.18257481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM2F	NM_017561.2	c.1840C>A	p.Leu614Ile	missense_variant	Exon 7 of 7	ENST00000253262.9	NP_060031.1
LOC105376154	XR_001746842.3	n.607+3886G>T		intron_variant	Intron 2 of 2
LOC105376154	XR_930132.4	n.190+3886G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUTM2F	ENST00000253262.9	c.1840C>A	p.Leu614Ile	missense_variant	Exon 7 of 7	1	NM_017561.2	ENSP00000253262.4

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1456782 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724506

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.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1840C>A (p.L614I) alteration is located in exon 7 (coding exon 7) of the NUTM2F gene. This alteration results from a C to A substitution at nucleotide position 1840, causing the leucine (L) at amino acid position 614 to be replaced by an isoleucine (I). 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	0.091
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.048
Sift	Benign	0.056	T;T
Sift4G	Benign	0.22	T;T
Polyphen		1.0	D;.
Vest4		0.15
MutPred		0.13		Gain of methylation at K609 (P = 0.0446);.;
MVP		0.030
ClinPred		0.38	T
GERP RS		0.51
Varity_R		0.070
gMVP		0.043

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs763606215; hg19: chr9-97081178;