10-87228529-G-T

Variant names:

• chr10-87228529-G-T
• rs755970841
• NM_001099338.2:c.649G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001099338.2(NUTM2A):​c.649G>T​(p.Ala217Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 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. A217T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2A NM_001099338.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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=0.05038309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM2A	NM_001099338.2	c.649G>T	p.Ala217Ser	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.649G>T	p.Ala217Ser	missense_variant	Exon 2 of 7	1	NM_001099338.2	ENSP00000371126.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152028 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1457400 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 724950

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1 AN: 152028 Hom.: 0 Cov.: 26 AF XY: 0.0000135 AC XY: 1 AN XY: 74252

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.57
DANN	Benign	0.16
DEOGEN2	Benign	0.00040	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00095	N
LIST_S2	Benign	0.27	T;T
M_CAP	Benign	0.00095	T
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.46	N;N
REVEL	Benign	0.011
Sift	Benign	0.68	T;T
Sift4G	Benign	0.61	T;T
Polyphen		0.0010	B;.
Vest4		0.14
MutPred		0.20		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.043
ClinPred		0.041	T
GERP RS		-1.0
Varity_R		0.031
gMVP		0.057

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs755970841; hg19: chr10-88988286;