rs1249698181

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-87228628-G-C
• chr10-87228628-G-A

Variant summary

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

The NM_001099338.2(NUTM2A):​c.748G>C​(p.Ala250Pro) 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 0.000027 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000066 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2A NM_001099338.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17004359).

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>C	p.Ala250Pro	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>C	p.Ala250Pro	missense	Exon 2 of 7	ENSP00000371126.1	Q8IVF1-1
	NUTM2A	ENST00000381689.4	TSL:5	c.748G>C	p.Ala250Pro	missense	Exon 2 of 7	ENSP00000371107.3	Q8IVF1-2
	NUTM2A-AS1	ENST00000446751.6	TSL:2	n.5344+12554C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 4 AN: 150248 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

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: 0.0000595

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000176 AC: 1 AN: 56770 AF XY: 0.00

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: 0.0000453

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000655 AC: 87 AN: 1327292 Hom.: 0 Cov.: 28 AF XY: 0.0000611 AC XY: 40 AN XY: 654490

⚠️ 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: 30154

American (AMR) AF: 0.00 AC: 0 AN: 34564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23036

East Asian (EAS) AF: 0.00 AC: 0 AN: 36416

South Asian (SAS) AF: 0.00 AC: 0 AN: 74728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3838

European-Non Finnish (NFE) AF: 0.0000793 AC: 81 AN: 1021830

Other (OTH) AF: 0.000109 AC: 6 AN: 55288

⚠️ 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: 0.0000266 AC: 4 AN: 150248 Hom.: 0 Cov.: 26 AF XY: 0.0000409 AC XY: 3 AN XY: 73270

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

African (AFR) AF: 0.00 AC: 0 AN: 40830

American (AMR) AF: 0.00 AC: 0 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000595 AC: 4 AN: 67272

Other (OTH) AF: 0.00 AC: 0 AN: 2056

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000000000310862), 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	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
PhyloP100		1.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.15
Sift	Benign	0.18	T
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.34
MutPred		0.42		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.40
ClinPred		0.24	T
GERP RS		-1.6
Varity_R		0.18
gMVP		0.10
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: rs1249698181; hg19: chr10-88988385;