rs747487158

Variant names:

• chr3-161242543-C-A
• rs747487158
• NM_015938.5:c.907C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-161242543-C-A
• chr3-161242543-C-G
• chr3-161242543-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015938.5(NMD3):​c.907C>A​(p.Pro303Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P303A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NMD3 NM_015938.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.40
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.927

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.907C>A	p.Pro303Thr	missense	Exon 11 of 16	NP_057022.2
	NMD3	NM_001320227.2		c.907C>A	p.Pro303Thr	missense	Exon 11 of 17	NP_001307156.1	C9JA08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMD3	ENST00000351193.7	TSL:1 MANE Select	c.907C>A	p.Pro303Thr	missense	Exon 11 of 16	ENSP00000307525.2	Q96D46
	NMD3	ENST00000472947.5	TSL:1	c.907C>A	p.Pro303Thr	missense	Exon 11 of 17	ENSP00000417559.1	C9JA08
	NMD3	ENST00000460469.1	TSL:1	c.907C>A	p.Pro303Thr	missense	Exon 10 of 15	ENSP00000419004.1	Q96D46

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251216 AF XY: 0.00

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: 0.00000137 AC: 2 AN: 1461174 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726912

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86194

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111540

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.32	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		7.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.79	P
Vest4		0.89
MutPred		0.77		Loss of catalytic residue at P303 (P = 0.04)
MVP		0.70
MPC		0.30
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.63
gMVP		0.63
Mutation Taster		=44/56	disease causing

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: rs747487158; hg19: chr3-160960331;