10-87228352-G-C

Variant names:

• chr10-87228352-G-C
• rs533509950
• NM_001099338.2:c.472G>C

Variant summary

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

The NM_001099338.2(NUTM2A):​c.472G>C​(p.Gly158Arg) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G158S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2A NM_001099338.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 0 publications found

Genes affected

NUTM2A (HGNC:23438): (NUT family member 2A)

NUTM2A-AS1 (HGNC:45161): (NUTM2A antisense RNA 1)

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=0.09123725).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099338.2. 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
	NUTM2A	NM_001099338.2	MANE Select	c.472G>C	p.Gly158Arg	missense	Exon 2 of 7	NP_001092808.1	Q8IVF1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUTM2A	ENST00000381707.6	TSL:1 MANE Select	c.472G>C	p.Gly158Arg	missense	Exon 2 of 7	ENSP00000371126.1	Q8IVF1-1
	NUTM2A	ENST00000381689.4	TSL:5	c.472G>C	p.Gly158Arg	missense	Exon 2 of 7	ENSP00000371107.3	Q8IVF1-2
	NUTM2A-AS1	ENST00000446751.6	TSL:2	n.5344+12830C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.00000432 AC: 1 AN: 231424 AF XY: 0.00000787

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.86e-7 AC: 1 AN: 1458594 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725602

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

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111434

Other (OTH) AF: 0.00 AC: 0 AN: 60166

⚠️ 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.: 21

ExAC AF: 0.00000854 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.8
DANN	Benign	0.74
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.10
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.022
Sift	Benign	0.14	T
Sift4G	Uncertain	0.054	T
Polyphen		0.23	B
Vest4		0.26
MutPred		0.21		Gain of methylation at G158 (P = 0.0391)
MVP		0.043
ClinPred		0.14	T
GERP RS		0.33
Varity_R		0.12
gMVP		0.12
Mutation Taster		=97/3	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: rs533509950; hg19: chr10-88988109;