10-87228352-G-A

Variant names:

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

Variant summary

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

The NM_001099338.2(NUTM2A):​c.472G>A​(p.Gly158Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (1 hom., cov: 21)
  • Exomes 𝑓: 0.00053 (10 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2A NM_001099338.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019382864).

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>A	p.Gly158Ser	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>A	p.Gly158Ser	missense	Exon 2 of 7	ENSP00000371126.1	Q8IVF1-1
	NUTM2A	ENST00000381689.4	TSL:5	c.472G>A	p.Gly158Ser	missense	Exon 2 of 7	ENSP00000371107.3	Q8IVF1-2
	NUTM2A-AS1	ENST00000446751.6	TSL:2	n.5344+12830C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152096 Hom.: 1 Cov.: 21

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000633

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000359 AC: 83 AN: 231424 AF XY: 0.000315

Gnomad AFR exome AF: 0.000155

Gnomad AMR exome AF: 0.000684

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000571

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000468

Gnomad OTH exome AF: 0.00124

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000531 AC: 775 AN: 1458518 Hom.: 10 Cov.: 32 AF XY: 0.000518 AC XY: 376 AN XY: 725568

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

African (AFR) AF: 0.000120 AC: 4 AN: 33402

American (AMR) AF: 0.000739 AC: 33 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26116

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86016

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

Middle Eastern (MID) AF: 0.000484 AC: 2 AN: 4134

European-Non Finnish (NFE) AF: 0.000630 AC: 700 AN: 1111372

Other (OTH) AF: 0.000465 AC: 28 AN: 60164

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.000368 AC: 56 AN: 152212 Hom.: 1 Cov.: 21 AF XY: 0.000363 AC XY: 27 AN XY: 74432

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

African (AFR) AF: 0.000168 AC: 7 AN: 41564

American (AMR) AF: 0.000261 AC: 4 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000633 AC: 43 AN: 67942

Other (OTH) AF: 0.00 AC: 0 AN: 2112

⚠️ 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: 0.000288 Hom.: 0

ExAC AF: 0.000256 AC: 30

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	0.087
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.6
DANN	Benign	0.87
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.10
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.014
Sift	Benign	0.16	T
Sift4G	Benign	0.24	T
Polyphen		0.050	B
Vest4		0.11
MVP		0.043
ClinPred		0.0033	T
GERP RS		0.33
Varity_R		0.047
gMVP		0.15
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: rs533509950; hg19: chr10-88988109; COSMIC: COSV67742022;