9-96932295-C-T

Variant names:

• chr9-96932295-C-T
• rs377255611
• NM_001170741.3:c.590C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001170741.3(NUTM2G):​c.590C>T​(p.Pro197Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000546 in 1,613,134 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. P197R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: NUTM2G NM_001170741.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.847
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008393317).

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.590C>T	p.Pro197Leu	missense	Exon 2 of 7	NP_001164212.1	Q5VZR2-1
	NUTM2G	NM_001045477.4		c.590C>T	p.Pro197Leu	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.590C>T	p.Pro197Leu	missense	Exon 2 of 7	ENSP00000361397.3	Q5VZR2-1
	NUTM2G	ENST00000354649.7	TSL:5	c.590C>T	p.Pro197Leu	missense	Exon 2 of 7	ENSP00000346670.2	Q5VZR2-2
	MFSD14CP	ENST00000506067.1	TSL:5	n.302+1500G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00253 AC: 385 AN: 152210 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00787

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000637 AC: 156 AN: 244734 AF XY: 0.000584

Gnomad AFR exome AF: 0.00701

Gnomad AMR exome AF: 0.000466

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.000172

Gnomad OTH exome AF: 0.000672

GnomAD4 exome AF: 0.000340 AC: 497 AN: 1460806 Hom.: 0 Cov.: 34 AF XY: 0.000333 AC XY: 242 AN XY: 726692

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

African (AFR) AF: 0.00718 AC: 240 AN: 33414

American (AMR) AF: 0.000716 AC: 32 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000406 AC: 35 AN: 86218

European-Finnish (FIN) AF: 0.0000752 AC: 4 AN: 53222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 0.000132 AC: 147 AN: 1111616

Other (OTH) AF: 0.000630 AC: 38 AN: 60312

⚠️ 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 AF: 0.00252 AC: 384 AN: 152328 Hom.: 1 Cov.: 31 AF XY: 0.00266 AC XY: 198 AN XY: 74488

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

African (AFR) AF: 0.00782 AC: 325 AN: 41558

American (AMR) AF: 0.00281 AC: 43 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68036

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000528 Hom.: 0

ESP6500AA AF: 0.00162 AC: 6

ESP6500EA AF: 0.000123 AC: 1

ExAC AF: 0.000896 AC: 108

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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	0.077
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.095
DANN	Benign	0.43
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.0084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		-0.85
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.0080
Sift	Benign	0.19	T
Sift4G	Benign	0.21	T
Polyphen		0.0070	B
Vest4		0.086
MVP		0.030
ClinPred		0.0057	T
GERP RS		-2.1
Varity_R		0.031
gMVP		0.046
Mutation Taster		=100/0	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: rs377255611; hg19: chr9-99694577; COSMIC: COSV100672867; COSMIC: COSV100672867;