Variant 7-156949771-C-T 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.34C>T(p.Pro12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,250,348 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: 0.000013 ( 0 hom. )

Consequence

NOM1
NM_138400.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.397

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=0.062814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOM1	NM_138400.2 linkuse as main transcript	c.34C>T	p.Pro12Ser	missense_variant	1/11	ENST00000275820.4	NP_612409.1	Q5C9Z4
NOM1	NM_001353366.2 linkuse as main transcript	c.34C>T	p.Pro12Ser	missense_variant	1/11		NP_001340295.1
NOM1	XR_927511.4 linkuse as main transcript	n.60C>T		non_coding_transcript_exon_variant	1/8
NOM1	XR_927513.4 linkuse as main transcript	n.60C>T		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.34C>T	p.Pro12Ser	missense_variant	1/11	1	NM_138400.2	ENSP00000275820.3		Q5C9Z4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1250348

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

605132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000132

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:

0.0000128

Gnomad4 OTH exome

AF:

0.0000194

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

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 17, 2021

The c.34C>T (p.P12S) alteration is located in exon 1 (coding exon 1) of the NOM1 gene. This alteration results from a C to T substitution at nucleotide position 34, causing the proline (P) at amino acid position 12 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

0.071

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.9

DANN

Benign

0.78

DEOGEN2

Benign

0.0038

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.38

M_CAP

Benign

0.0067

MetaRNN

Benign

0.063

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.16

REVEL

Benign

0.011

Sift

Pathogenic

0.0

Sift4G

Benign

0.44

Polyphen

0.079

Vest4

0.068

MutPred

0.32

Gain of phosphorylation at P12 (P = 0.0068);

MVP

0.14

MPC

1.6

ClinPred

0.23

GERP RS

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.046

gMVP

0.14

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

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