Variant 3-161242543-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015938.5(NMD3):c.907C>T(p.Pro303Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

NMD3
NM_015938.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.40

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 made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMD3	NM_015938.5 linkuse as main transcript	c.907C>T	p.Pro303Ser	missense_variant	11/16	ENST00000351193.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NMD3	ENST00000351193.7 linkuse as main transcript	c.907C>T	p.Pro303Ser	missense_variant	11/16	1	NM_015938.5	P1
NMD3	ENST00000472947.5 linkuse as main transcript	c.907C>T	p.Pro303Ser	missense_variant	11/17	1
NMD3	ENST00000460469.1 linkuse as main transcript	c.907C>T	p.Pro303Ser	missense_variant	10/15	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251216

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000868

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461174

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726912

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000894

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:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151972

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.0000967

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

The c.907C>T (p.P303S) alteration is located in exon 11 (coding exon 10) of the NMD3 gene. This alteration results from a C to T substitution at nucleotide position 907, causing the proline (P) at amino acid position 303 to be replaced by a serine (S). 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

0.15

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Uncertain

-0.080

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.025

MetaRNN

Pathogenic

0.84

D;D;D

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.4

M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-5.9

D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.023

D;T;D

Sift4G

Benign

0.070

T;T;T

Polyphen

0.062

B;B;B

Vest4

0.79

MutPred

0.78

Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);

MVP

0.63

MPC

0.11

ClinPred

0.79

GERP RS

4.5

Varity_R

0.51

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over