10-87228565-C-A

Variant names:

• chr10-87228565-C-A
• rs571729371
• NM_001099338.2:c.685C>A

Variant summary

Our verdict is Likely benign. Variant got -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. 12/19 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

Genes affected

NUTM2A (HGNC:23438): (NUT family member 2A)

NUTM2A-AS1 (HGNC:45161): (NUTM2A antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05296117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM2A	NM_001099338.2	c.685C>A	p.Leu229Ile	missense_variant	Exon 2 of 7	ENST00000381707.6	NP_001092808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUTM2A	ENST00000381707.6	c.685C>A	p.Leu229Ile	missense_variant	Exon 2 of 7	1	NM_001099338.2	ENSP00000371126.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 36 AN: 151616 Hom.: 0 Cov.: 26 FAILED QC

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

GnomAD3 exomes AF: 0.000225 AC: 18 AN: 79980 Hom.: 0 AF XY: 0.000269 AC XY: 11 AN XY: 40928

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 SAS exome AF: 0.000384

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

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000203

Gnomad4 ASJ exome AF: 0.000616

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00111

Gnomad4 FIN exome AF: 0.0000571

Gnomad4 NFE exome AF: 0.000191

Gnomad4 OTH exome AF: 0.000150

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

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000369

Gnomad4 OTH AF: 0.000476

Alfa AF: 0.000278 Hom.: 0

ExAC AF: 0.0000685 AC: 7

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.685C>A (p.L229I) alteration is located in exon 2 (coding exon 2) of the NUTM2A gene. This alteration results from a C to A substitution at nucleotide position 685, causing the leucine (L) at amino acid position 229 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-0.85	T
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.061
Sift	Benign	0.10	T;T
Sift4G	Benign	0.15	T;T
Polyphen		1.0	D;.
Vest4		0.24
MutPred		0.47		Loss of catalytic residue at L229 (P = 0.0094);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs571729371; hg19: chr10-88988322;