9-94318827-G-A

Variant names:

• chr9-94318827-G-A
• rs748125837
• NM_017561.2:c.1909C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017561.2(NUTM2F):​c.1909C>T​(p.Pro637Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2F NM_017561.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.397
• Publications: 0 publications found

Genes affected

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

LOC105376154 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08386552).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017561.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUTM2F	NM_017561.2	MANE Select	c.1909C>T	p.Pro637Ser	missense	Exon 7 of 7	NP_060031.1	A1L443

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUTM2F	ENST00000253262.9	TSL:1 MANE Select	c.1909C>T	p.Pro637Ser	missense	Exon 7 of 7	ENSP00000253262.4	A1L443

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.0000506 AC: 8 AN: 157950 AF XY: 0.0000476

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000662

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000126 AC: 18 AN: 1428732 Hom.: 0 Cov.: 31 AF XY: 0.0000113 AC XY: 8 AN XY: 708652

African (AFR) AF: 0.00 AC: 0 AN: 32912

American (AMR) AF: 0.00 AC: 0 AN: 39474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25506

East Asian (EAS) AF: 0.000413 AC: 16 AN: 38696

South Asian (SAS) AF: 0.00 AC: 0 AN: 83180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5334

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092590

Other (OTH) AF: 0.0000169 AC: 1 AN: 59224

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000175 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.1
DANN	Benign	0.91
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.40
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.037
Sift	Benign	0.60	T
Sift4G	Benign	0.21	T
Polyphen		0.82	P
Vest4		0.14
MutPred		0.15		Loss of loop (P = 0.0128)
MVP		0.014
ClinPred		0.13	T
GERP RS		1.5
Varity_R		0.091
gMVP		0.12
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs748125837; hg19: chr9-97081109; COSMIC: COSV105873232;