NM_001099338.2:c.685C>A

Variant names:

• chr10-87228565-C-A
• rs571729371
• NM_001099338.2:c.685C>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.685C>A​(p.Leu229Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.00024 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00024 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2A NM_001099338.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.382
• 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=0.05296117).

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.685C>A	p.Leu229Ile	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.685C>A	p.Leu229Ile	missense	Exon 2 of 7	ENSP00000371126.1	Q8IVF1-1
	NUTM2A	ENST00000381689.4	TSL:5	c.685C>A	p.Leu229Ile	missense	Exon 2 of 7	ENSP00000371107.3	Q8IVF1-2
	NUTM2A-AS1	ENST00000446751.6	TSL:2	n.5344+12617G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 151616 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000369

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.000225 AC: 18 AN: 79980 AF XY: 0.000269

Gnomad AFR exome AF: 0.000160

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.000468

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000253

Gnomad OTH exome AF: 0.000419

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000242 AC: 351 AN: 1453186 Hom.: 7 Cov.: 35 AF XY: 0.000287 AC XY: 207 AN XY: 722490

⚠️ 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: 33218

American (AMR) AF: 0.000203 AC: 9 AN: 44274

Ashkenazi Jewish (ASJ) AF: 0.000616 AC: 16 AN: 25962

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00111 AC: 95 AN: 85708

European-Finnish (FIN) AF: 0.0000571 AC: 3 AN: 52582

Middle Eastern (MID) AF: 0.000729 AC: 3 AN: 4116

European-Non Finnish (NFE) AF: 0.000191 AC: 212 AN: 1107786

Other (OTH) AF: 0.000150 AC: 9 AN: 59868

⚠️ 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: 0.000237 AC: 36 AN: 151734 Hom.: 0 Cov.: 26 AF XY: 0.000297 AC XY: 22 AN XY: 74162

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

African (AFR) AF: 0.0000483 AC: 2 AN: 41442

American (AMR) AF: 0.000262 AC: 4 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4784

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10558

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

European-Non Finnish (NFE) AF: 0.000369 AC: 25 AN: 67734

Other (OTH) AF: 0.000476 AC: 1 AN: 2102

⚠️ 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: 0.000278 Hom.: 0

ExAC AF: 0.0000685 AC: 7

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	-0.41	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.85	T
PhyloP100		0.38
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.061
Sift	Benign	0.10	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.24
MutPred		0.47		Loss of catalytic residue at L229 (P = 0.0094)
MVP		0.082
ClinPred		0.022	T
GERP RS		-1.4
Varity_R		0.051
gMVP		0.037
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: rs571729371; hg19: chr10-88988322;