9-96932337-G-C

Variant names:

• chr9-96932337-G-C
• rs769089742
• NM_001170741.3:c.632G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001170741.3(NUTM2G):​c.632G>C​(p.Arg211Pro) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R211Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2G NM_001170741.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98
• Publications: 0 publications found

Genes affected

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

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]

MFSD14CP (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170741.3. 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
	NUTM2G	NM_001170741.3	MANE Select	c.632G>C	p.Arg211Pro	missense	Exon 2 of 7	NP_001164212.1	Q5VZR2-1
	NUTM2G	NM_001045477.4		c.632G>C	p.Arg211Pro	missense	Exon 2 of 7	NP_001038942.1	Q5VZR2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUTM2G	ENST00000372322.4	TSL:5 MANE Select	c.632G>C	p.Arg211Pro	missense	Exon 2 of 7	ENSP00000361397.3	Q5VZR2-1
	NUTM2G	ENST00000354649.7	TSL:5	c.632G>C	p.Arg211Pro	missense	Exon 2 of 7	ENSP00000346670.2	Q5VZR2-2
	MFSD14CP	ENST00000506067.1	TSL:5	n.302+1458C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000823 AC: 2 AN: 242930 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000184

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000151 AC: 22 AN: 1459856 Hom.: 0 Cov.: 34 AF XY: 0.0000193 AC XY: 14 AN XY: 726194

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4946

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111572

Other (OTH) AF: 0.0000166 AC: 1 AN: 60250

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000480 Hom.: 0

ExAC AF: 0.0000166 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	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.078
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0033	T
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		3.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.98	D
Vest4		0.71
MutPred		0.77		Loss of MoRF binding (P = 5e-04)
MVP		0.17
ClinPred		0.94	D
GERP RS		1.0
Varity_R		0.75
gMVP		0.45
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs769089742; hg19: chr9-99694619;