Variant 10-102157514-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004741.5(NOLC1):c.400G>A(p.Asp134Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NOLC1
NM_004741.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.22

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20216933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOLC1	NM_004741.5 link	c.400G>A	p.Asp134Asn	missense_variant	Exon 4 of 13	ENST00000605788.6	NP_004732.2	Q14978-1Q96J17B2RAU8
NOLC1	NM_001284388.2 link	c.400G>A	p.Asp134Asn	missense_variant	Exon 4 of 13		NP_001271317.1	Q14978-2B2RAU8
NOLC1	NM_001284389.2 link	c.403G>A	p.Asp135Asn	missense_variant	Exon 4 of 13		NP_001271318.1	Q14978-3
NOLC1	XM_005270273.3 link	c.403G>A	p.Asp135Asn	missense_variant	Exon 4 of 13		XP_005270330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOLC1	ENST00000605788.6 link	c.400G>A	p.Asp134Asn	missense_variant	Exon 4 of 13	1	NM_004741.5	ENSP00000474710.2		Q14978-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461434

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727020

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

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 01, 2024

The c.400G>A (p.D134N) alteration is located in exon 4 (coding exon 4) of the NOLC1 gene. This alteration results from a G to A substitution at nucleotide position 400, causing the aspartic acid (D) at amino acid position 134 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

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;.;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Pathogenic

3.0

M;M;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.1

.;N;.

REVEL

Benign

0.099

Sift

Uncertain

0.0070

.;D;.

Sift4G

Uncertain

0.035

D;D;D

Polyphen

0.80

P;P;P

Vest4

0.35

MutPred

0.14

Loss of stability (P = 0.0239);Loss of stability (P = 0.0239);.;

MVP

0.63

MPC

0.13

ClinPred

0.94

GERP RS

4.5

Varity_R

0.18

gMVP

0.16

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