Variant 6-30547244-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005275.5(GNL1):c.1309A>C(p.Ile437Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,456,968 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: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

GNL1
NM_005275.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

Variant links:

Genes affected

GNL1 (HGNC:4413): (G protein nucleolar 1 (putative)) The GNL1 gene, identified in the human major histocompatibility complex class I region, shows a high degree of similarity with its mouse counterpart. The GNL1 gene is located less than 2 kb centromeric to HLA-E, in the same transcriptional orientation. GNL1 is telomeric to HLA-B and HLA-C. [provided by RefSeq, Jul 2008]

GNL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06038946).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNL1	NM_005275.5 linkuse as main transcript	c.1309A>C	p.Ile437Leu	missense_variant	10/12	ENST00000376621.8	NP_005266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNL1	ENST00000376621.8 linkuse as main transcript	c.1309A>C	p.Ile437Leu	missense_variant	10/12	1	NM_005275.5	ENSP00000365806	P1	P36915-1
GNL1	ENST00000464231.1 linkuse as main transcript	n.497A>C		non_coding_transcript_exon_variant	2/2	1
GNL1	ENST00000462708.1 linkuse as main transcript	n.290A>C		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242436

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131864

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:

0.00000917

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1456968

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724636

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:

0.00000721

Gnomad4 OTH exome

AF:

0.00

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

Jan 06, 2023

The c.1309A>C (p.I437L) alteration is located in exon 10 (coding exon 10) of the GNL1 gene. This alteration results from a A to C substitution at nucleotide position 1309, causing the isoleucine (I) at amino acid position 437 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.020

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.66

M_CAP

Benign

0.0033

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.030

MutationTaster

Benign

0.96

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.40

REVEL

Benign

0.054

Sift

Benign

0.85

Sift4G

Benign

0.91

Polyphen

0.0

Vest4

0.16

MutPred

0.47

Gain of glycosylation at P440 (P = 0.0983);

MVP

0.12

MPC

0.65

ClinPred

0.051

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.11

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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