Genetic Variant NM_015938.5:c.68C>T (chr3-161224953-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015938.5(NMD3):c.68C>T(p.Pro23Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,612,006 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 1 hom. )

Consequence

NMD3
NM_015938.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

Publications

1 publications found

Variant links:

Genes affected

NMD3 (HGNC:24250): (NMD3 ribosome export adaptor) Ribosomal 40S and 60S subunits associate in the nucleolus and are exported to the cytoplasm. The protein encoded by this gene is involved in the passage of the 60S subunit through the nuclear pore complex and into the cytoplasm. Several transcript variants exist for this gene, but the full-length natures of only two have been described to date. [provided by RefSeq, Feb 2016]

NMD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11233738).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015938.5. 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
	NMD3	NM_015938.5	MANE Select	c.68C>T	p.Pro23Leu	missense	Exon 3 of 16	NP_057022.2
	NMD3	NM_001320227.2		c.68C>T	p.Pro23Leu	missense	Exon 3 of 17	NP_001307156.1	C9JA08

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NMD3	ENST00000351193.7	TSL:1 MANE Select	c.68C>T	p.Pro23Leu	missense	Exon 3 of 16	ENSP00000307525.2	Q96D46
NMD3	ENST00000472947.5	TSL:1	c.68C>T	p.Pro23Leu	missense	Exon 3 of 17	ENSP00000417559.1	C9JA08
NMD3	ENST00000460469.1	TSL:1	c.68C>T	p.Pro23Leu	missense	Exon 2 of 15	ENSP00000419004.1	Q96D46

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151602

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000728

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000480

AC:

AN:

249934

AF XY:

0.0000592

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000247

AC:

AN:

1460286

Hom.:

Cov.:

AF XY:

0.0000372

AC XY:

AN XY:

726456

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33368

American (AMR)

AF:

0.00

AC:

AN:

44486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39560

South Asian (SAS)

AF:

0.000326

AC:

AN:

86012

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111270

Other (OTH)

AF:

0.00

AC:

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151720

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74092

show subpopulations

African (AFR)

AF:

0.0000726

AC:

AN:

41332

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.000208

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67936

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.097

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.028

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

1.9

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-5.4

REVEL

Benign

0.063

Sift

Benign

0.076

Sift4G

Benign

0.080

Polyphen

0.74

Vest4

0.35

MVP

0.43

MPC

0.24

ClinPred

0.36

GERP RS

2.0

Varity_R

0.090

gMVP

0.50

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over