Variant 3-161234786-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015938.5(NMD3):c.417A>C(p.Gln139His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,098 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NMD3
NM_015938.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.558

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:

NMD3 (HGNC:):

NMD3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMD3	NM_015938.5 linkuse as main transcript	c.417A>C	p.Gln139His	missense_variant	6/16	ENST00000351193.7	NP_057022.2	Q96D46

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMD3	ENST00000351193.7 linkuse as main transcript	c.417A>C	p.Gln139His	missense_variant	6/16	1	NM_015938.5	ENSP00000307525.2		Q96D46

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461098

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726886

show subpopulations

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

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

Apr 23, 2024

The c.417A>C (p.Q139H) alteration is located in exon 6 (coding exon 5) of the NMD3 gene. This alteration results from a A to C substitution at nucleotide position 417, causing the glutamine (Q) at amino acid position 139 to be replaced by a histidine (H). 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

0.34

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.092

.;T;T;.;T;T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.81

LIST_S2

Pathogenic

0.97

D;.;.;D;D;D;D

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.58

D;D;D;D;D;D;D

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.7

.;.;L;.;.;.;L

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-4.2

D;D;D;D;D;D;D

REVEL

Uncertain

0.35

Sift

Benign

0.14

T;T;T;T;T;T;T

Sift4G

Benign

0.26

T;T;T;T;T;T;T

Polyphen

1.0, 0.94

.;.;D;P;.;.;D

Vest4

0.86, 0.87

MutPred

0.63

Gain of catalytic residue at D143 (P = 0.1685);Gain of catalytic residue at D143 (P = 0.1685);Gain of catalytic residue at D143 (P = 0.1685);Gain of catalytic residue at D143 (P = 0.1685);Gain of catalytic residue at D143 (P = 0.1685);Gain of catalytic residue at D143 (P = 0.1685);Gain of catalytic residue at D143 (P = 0.1685);

MVP

0.46

MPC

0.42

ClinPred

0.98

GERP RS

-7.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.60

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

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

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