Variant 7-156950110-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138400.2(NOM1):c.373G>A(p.Asp125Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000643 in 1,400,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

NOM1
NM_138400.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.148

Variant links:

Genes affected

NOM1 (HGNC:13244): (nucleolar protein with MIF4G domain 1) Proteins that contain MIF4G (middle of eIF4G (MIM 600495)) and/or MA3 domains, such as NOM1, function in protein translation. These domains include binding sites for members of the EIF4A family of ATP-dependent DEAD box RNA helicases (see EIF4A1; MIM 602641) (Simmons et al., 2005 [PubMed 15715967]).[supplied by OMIM, Mar 2008]

NOM1 links:

NOM1 (HGNC:):

NOM1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053133935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOM1	NM_138400.2 linkuse as main transcript	c.373G>A	p.Asp125Asn	missense_variant	1/11	ENST00000275820.4	NP_612409.1	Q5C9Z4
NOM1	NM_001353366.2 linkuse as main transcript	c.373G>A	p.Asp125Asn	missense_variant	1/11		NP_001340295.1
NOM1	XR_927511.4 linkuse as main transcript	n.399G>A		non_coding_transcript_exon_variant	1/8
NOM1	XR_927513.4 linkuse as main transcript	n.399G>A		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOM1	ENST00000275820.4 linkuse as main transcript	c.373G>A	p.Asp125Asn	missense_variant	1/11	1	NM_138400.2	ENSP00000275820.3		Q5C9Z4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000643

AC:

AN:

1400148

Hom.:

Cov.:

AF XY:

0.00000867

AC XY:

AN XY:

691962

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:

0.0000985

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

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

Sep 27, 2022

The c.373G>A (p.D125N) alteration is located in exon 1 (coding exon 1) of the NOM1 gene. This alteration results from a G to A substitution at nucleotide position 373, causing the aspartic acid (D) at amino acid position 125 to be replaced by an asparagine (N). 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

0.091

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.4

DANN

Benign

0.93

DEOGEN2

Benign

0.0042

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.48

M_CAP

Benign

0.0054

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.16

REVEL

Benign

0.054

Sift

Benign

0.57

Sift4G

Benign

0.30

Polyphen

0.072

Vest4

0.076

MutPred

0.21

Gain of MoRF binding (P = 0.084);

MVP

0.23

MPC

0.91

ClinPred

0.072

GERP RS

2.5

Varity_R

0.042

gMVP

0.069

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over