10-87228482-C-G

Variant names:

• chr10-87228482-C-G
• rs762216564
• NM_001099338.2:c.602C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099338.2(NUTM2A):​c.602C>G​(p.Ser201Cys) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.000010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2A NM_001099338.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06094438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM2A	NM_001099338.2	c.602C>G	p.Ser201Cys	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.602C>G	p.Ser201Cys	missense_variant	Exon 2 of 7	1	NM_001099338.2	ENSP00000371126.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD3 exomes AF: 0.00000857 AC: 2 AN: 233470 Hom.: 0 AF XY: 0.00000782 AC XY: 1 AN XY: 127934

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000103 AC: 15 AN: 1458028 Hom.: 0 Cov.: 35 AF XY: 0.0000110 AC XY: 8 AN XY: 725308

Gnomad4 AFR exome AF: 0.0000300

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: 0.0000108

Gnomad4 OTH exome AF: 0.0000333

GnomAD4 genome Cov.: 26

ExAC AF: 0.00000852 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.602C>G (p.S201C) alteration is located in exon 2 (coding exon 2) of the NUTM2A gene. This alteration results from a C to G substitution at nucleotide position 602, causing the serine (S) at amino acid position 201 to be replaced by a cysteine (C). 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	0.097
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.47
DANN	Benign	0.64
DEOGEN2	Benign	0.0028	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00024	N
LIST_S2	Benign	0.069	T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.019
Sift	Benign	0.15	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.046	B;.
Vest4		0.11
MutPred		0.41		Loss of disorder (P = 0.0236);Loss of disorder (P = 0.0236);
MVP		0.043
ClinPred		0.032	T
GERP RS		-2.6
Varity_R		0.052
gMVP		0.066

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: rs762216564; hg19: chr10-88988239;