rs1242333698

Variant names:

• chr10-87228734-C-T
• rs1242333698
• NM_001099338.2:c.854C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001099338.2(NUTM2A):​c.854C>T​(p.Pro285Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 140,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000052 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2A NM_001099338.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.649
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.118821084).

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.854C>T	p.Pro285Leu	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.854C>T	p.Pro285Leu	missense	Exon 2 of 7	ENSP00000371126.1	Q8IVF1-1
	NUTM2A	ENST00000381689.4	TSL:5	c.854C>T	p.Pro285Leu	missense	Exon 2 of 7	ENSP00000371107.3	Q8IVF1-2
	NUTM2A-AS1	ENST00000446751.6	TSL:2	n.5344+12448G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000923 AC: 13 AN: 140840 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000759

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: 0.0000157

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000158 AC: 9 AN: 56874 AF XY: 0.000105

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000529

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000251

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000462

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000516 AC: 44 AN: 852454 Hom.: 0 Cov.: 12 AF XY: 0.0000349 AC XY: 15 AN XY: 429534

⚠️ 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: 20040

American (AMR) AF: 0.000325 AC: 9 AN: 27700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17144

East Asian (EAS) AF: 0.0000889 AC: 3 AN: 33754

South Asian (SAS) AF: 0.0000175 AC: 1 AN: 57306

European-Finnish (FIN) AF: 0.0000287 AC: 1 AN: 34820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2784

European-Non Finnish (NFE) AF: 0.0000452 AC: 28 AN: 619260

Other (OTH) AF: 0.0000504 AC: 2 AN: 39646

⚠️ 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: 0.0000923 AC: 13 AN: 140920 Hom.: 0 Cov.: 24 AF XY: 0.0000879 AC XY: 6 AN XY: 68232

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

African (AFR) AF: 0.0000265 AC: 1 AN: 37758

American (AMR) AF: 0.000758 AC: 11 AN: 14512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3250

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.0000157 AC: 1 AN: 63658

Other (OTH) AF: 0.00 AC: 0 AN: 1894

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000759087), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000742 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	0.094
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.65
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.017
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.046	D
Polyphen		1.0	D
Vest4		0.24
MutPred		0.27		Loss of glycosylation at P285 (P = 0.0013)
MVP		0.15
ClinPred		0.22	T
GERP RS		0.33
Varity_R		0.11
gMVP		0.11
Mutation Taster		=99/1	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: rs1242333698; hg19: chr10-88988491;