7-156950066-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_138400.2(NOM1):ā€‹c.329T>Cā€‹(p.Leu110Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,391,722 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 Likely benign (ā˜…).

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

NOM1
NM_138400.2 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.602
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.042176813).
BP6
Variant 7-156950066-T-C is Benign according to our data. Variant chr7-156950066-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3201132.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NOM1NM_138400.2 linkuse as main transcriptc.329T>C p.Leu110Pro missense_variant 1/11 ENST00000275820.4 NP_612409.1 Q5C9Z4
NOM1NM_001353366.2 linkuse as main transcriptc.329T>C p.Leu110Pro missense_variant 1/11 NP_001340295.1
NOM1XR_927511.4 linkuse as main transcriptn.355T>C non_coding_transcript_exon_variant 1/8
NOM1XR_927513.4 linkuse as main transcriptn.355T>C non_coding_transcript_exon_variant 1/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NOM1ENST00000275820.4 linkuse as main transcriptc.329T>C p.Leu110Pro missense_variant 1/111 NM_138400.2 ENSP00000275820.3 Q5C9Z4

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000144
AC:
2
AN:
1391722
Hom.:
0
Cov.:
33
AF XY:
0.00000146
AC XY:
1
AN XY:
686860
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:
0.0000345
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJul 06, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.038
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
6.9
DANN
Benign
0.58
DEOGEN2
Benign
0.0031
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.00019
N
LIST_S2
Benign
0.15
T
M_CAP
Benign
0.0084
T
MetaRNN
Benign
0.042
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-1.0
N
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
1.4
N
REVEL
Benign
0.067
Sift
Benign
0.29
T
Sift4G
Benign
0.28
T
Polyphen
0.0
B
Vest4
0.076
MutPred
0.21
Gain of relative solvent accessibility (P = 0.0166);
MVP
0.15
MPC
1.4
ClinPred
0.32
T
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.049
gMVP
0.073

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.

Other links and lift over

hg19: chr7-156742760; API