10-87228628-G-A

Variant names:

• chr10-87228628-G-A
• rs1249698181
• NM_001099338.2:c.748G>A

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.748G>A​(p.Ala250Thr) 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. 14/21 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. A250P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 26)
• Consequence: NUTM2A NM_001099338.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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=0.07111856).

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.748G>A	p.Ala250Thr	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.748G>A	p.Ala250Thr	missense	Exon 2 of 7	ENSP00000371126.1	Q8IVF1-1
	NUTM2A	ENST00000381689.4	TSL:5	c.748G>A	p.Ala250Thr	missense	Exon 2 of 7	ENSP00000371107.3	Q8IVF1-2
	NUTM2A-AS1	ENST00000446751.6	TSL:2	n.5344+12554C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.8
DANN	Benign	0.93
DEOGEN2	Benign	0.00053	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.033
Sift	Benign	1.0	T
Sift4G	Benign	0.54	T
Polyphen		0.33	B
Vest4		0.15
MutPred		0.38		Gain of glycosylation at A250 (P = 0.0017)
MVP		0.34
ClinPred		0.17	T
GERP RS		-1.6
Varity_R		0.033
gMVP		0.035
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: rs1249698181; hg19: chr10-88988385; COSMIC: COSV101095742;