Variant 10-102158077-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004741.5(NOLC1):c.470C>T(p.Ala157Val) 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 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NOLC1
NM_004741.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.938

Variant links:

Genes affected

NOLC1 (HGNC:15608): (nucleolar and coiled-body phosphoprotein 1) Enables protein heterodimerization activity and protein-macromolecule adaptor activity. Involved in neural crest cell development; neural crest formation; and regulation of translation. Located in fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

NOLC1 links:

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=0.043854326).

BP6

Variant 10-102158077-C-T is Benign according to our data. Variant chr10-102158077-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2330848.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOLC1	NM_004741.5 link	c.470C>T	p.Ala157Val	missense_variant	5/13	ENST00000605788.6	NP_004732.2	Q14978-1Q96J17B2RAU8
NOLC1	NM_001284388.2 link	c.470C>T	p.Ala157Val	missense_variant	5/13		NP_001271317.1	Q14978-2B2RAU8
NOLC1	NM_001284389.2 link	c.473C>T	p.Ala158Val	missense_variant	5/13		NP_001271318.1	Q14978-3
NOLC1	XM_005270273.3 link	c.473C>T	p.Ala158Val	missense_variant	5/13		XP_005270330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOLC1	ENST00000605788.6 link	c.470C>T	p.Ala157Val	missense_variant	5/13	1	NM_004741.5	ENSP00000474710.2		Q14978-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251360

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135844

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727188

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 submitter

clinical testing

Ambry Genetics

Dec 01, 2022

This 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

0.078

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.027

T;.;.;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.72

T;T;T;T

M_CAP

Benign

0.0082

MetaRNN

Benign

0.044

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.42

N;N;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.88

.;N;.;.

REVEL

Benign

0.029

Sift

Benign

0.80

.;T;.;.

Sift4G

Benign

0.92

T;T;T;T

Polyphen

0.0020

B;B;B;.

Vest4

0.065

MutPred

0.18

Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);.;.;

MVP

0.29

MPC

0.12

ClinPred

0.11

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.017

gMVP

0.10

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