10-79848858-T-C

Variant names:

• chr10-79848858-T-C
• rs766237452
• NM_001355263.2:c.1697T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001355263.2(NUTM2E):​c.1697T>C​(p.Ile566Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 8)
  • Exomes 𝑓: 0.0031 (43 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUTM2E NM_001355263.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.558
• Publications: 1 publications found

Genes affected

NUTM2E (HGNC:23448): (NUT family member 2E)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0051302016).
• BP6: Variant 10-79848858-T-C is Benign according to our data. Variant chr10-79848858-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2640651.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355263.2. 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
	NUTM2E	NM_001355263.2	MANE Select	c.1697T>C	p.Ile566Thr	missense	Exon 8 of 10	NP_001342192.1	B1AL46

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUTM2E	ENST00000429984.5	TSL:5 MANE Select	c.1697T>C	p.Ile566Thr	missense	Exon 8 of 10	ENSP00000407521.2	B1AL46
	NUTM2E	ENST00000602967.5	TSL:5	c.1697T>C	p.Ile566Thr	missense	Exon 5 of 6	ENSP00000473558.1	R4GNA6

Frequencies

GnomAD3 genomes AF: 0.00272 AC: 178 AN: 65402 Hom.: 1 Cov.: 8

Gnomad AFR AF: 0.000953

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00257

Gnomad ASJ AF: 0.00353

Gnomad EAS AF: 0.00239

Gnomad SAS AF: 0.000853

Gnomad FIN AF: 0.00542

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00384

Gnomad OTH AF: 0.00254

GnomAD2 exomes AF: 0.00365 AC: 186 AN: 51000 AF XY: 0.00334

Gnomad AFR exome AF: 0.00137

Gnomad AMR exome AF: 0.00274

Gnomad ASJ exome AF: 0.00601

Gnomad EAS exome AF: 0.00286

Gnomad FIN exome AF: 0.0106

Gnomad NFE exome AF: 0.00367

Gnomad OTH exome AF: 0.00844

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00306 AC: 1329 AN: 434610 Hom.: 43 Cov.: 4 AF XY: 0.00311 AC XY: 701 AN XY: 225652

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

African (AFR) AF: 0.00137 AC: 20 AN: 14638

American (AMR) AF: 0.00252 AC: 44 AN: 17454

Ashkenazi Jewish (ASJ) AF: 0.00221 AC: 25 AN: 11320

East Asian (EAS) AF: 0.00246 AC: 63 AN: 25588

South Asian (SAS) AF: 0.00265 AC: 125 AN: 47182

European-Finnish (FIN) AF: 0.00606 AC: 142 AN: 23442

Middle Eastern (MID) AF: 0.00937 AC: 17 AN: 1814

European-Non Finnish (NFE) AF: 0.00292 AC: 791 AN: 270734

Other (OTH) AF: 0.00455 AC: 102 AN: 22438

⚠️ 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 AF: 0.00272 AC: 178 AN: 65526 Hom.: 1 Cov.: 8 AF XY: 0.00305 AC XY: 98 AN XY: 32138

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

African (AFR) AF: 0.000949 AC: 19 AN: 20022

American (AMR) AF: 0.00255 AC: 17 AN: 6660

Ashkenazi Jewish (ASJ) AF: 0.00353 AC: 6 AN: 1698

East Asian (EAS) AF: 0.00240 AC: 7 AN: 2914

South Asian (SAS) AF: 0.000850 AC: 2 AN: 2352

European-Finnish (FIN) AF: 0.00542 AC: 25 AN: 4616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 122

European-Non Finnish (NFE) AF: 0.00384 AC: 100 AN: 26052

Other (OTH) AF: 0.00248 AC: 2 AN: 806

⚠️ 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: 0.00244 Hom.: 0

ExAC AF: 0.00175 AC: 120

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.56
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.058
Sift	Benign	0.069	T
Sift4G	Benign	0.14	T
Vest4		0.25
MVP		0.10
ClinPred		0.023	T
GERP RS		0.71
Varity_R		0.29
gMVP		0.046
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: rs766237452; hg19: chr10-81608614;