rs199718151

Variant names:

• chr10-87228559-G-A
• rs199718151
• NM_001099338.2:c.679G>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.679G>A​(p.Ala227Thr) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A227G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000074 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2A NM_001099338.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.303
• 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=0.051602364).

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.679G>A	p.Ala227Thr	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.679G>A	p.Ala227Thr	missense	Exon 2 of 7	ENSP00000371126.1	Q8IVF1-1
	NUTM2A	ENST00000381689.4	TSL:5	c.679G>A	p.Ala227Thr	missense	Exon 2 of 7	ENSP00000371107.3	Q8IVF1-2
	NUTM2A-AS1	ENST00000446751.6	TSL:2	n.5344+12623C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000397 AC: 6 AN: 151066 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000730

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000444

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000960 AC: 8 AN: 83330 AF XY: 0.0000935

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000233

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000114

Gnomad NFE exome AF: 0.0000601

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000745 AC: 108 AN: 1450196 Hom.: 4 Cov.: 35 AF XY: 0.0000791 AC XY: 57 AN XY: 721020

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

African (AFR) AF: 0.000483 AC: 16 AN: 33132

American (AMR) AF: 0.000113 AC: 5 AN: 44276

Ashkenazi Jewish (ASJ) AF: 0.0000388 AC: 1 AN: 25790

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39656

South Asian (SAS) AF: 0.000140 AC: 12 AN: 85720

European-Finnish (FIN) AF: 0.0000762 AC: 4 AN: 52500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4106

European-Non Finnish (NFE) AF: 0.0000525 AC: 58 AN: 1105238

Other (OTH) AF: 0.000184 AC: 11 AN: 59778

⚠️ 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: 0.0000463 AC: 7 AN: 151186 Hom.: 0 Cov.: 26 AF XY: 0.0000406 AC XY: 3 AN XY: 73876

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

African (AFR) AF: 0.0000970 AC: 4 AN: 41246

American (AMR) AF: 0.00 AC: 0 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10508

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

European-Non Finnish (NFE) AF: 0.0000444 AC: 3 AN: 67512

Other (OTH) AF: 0.00 AC: 0 AN: 2096

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000000000277556), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 Hom.: 0

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	0.091
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.1
DANN	Benign	0.85
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.30
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.023
Sift	Benign	0.91	T
Sift4G	Benign	0.93	T
Polyphen		0.036	B
Vest4		0.20
MutPred		0.34		Gain of sheet (P = 0.1451)
MVP		0.15
ClinPred		0.033	T
GERP RS		1.3
Varity_R		0.025
gMVP		0.047
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs199718151; hg19: chr10-88988316;