6-30553360-G-C

Variant names:

• chr6-30553360-G-C
• rs2074505
• NM_005275.5:c.798C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005275.5(GNL1):​c.798C>G​(p.Asp266Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GNL1 NM_005275.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060096443).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005275.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNL1	NM_005275.5	MANE Select	c.798C>G	p.Asp266Glu	missense	Exon 6 of 12	NP_005266.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNL1	ENST00000376621.8	TSL:1 MANE Select	c.798C>G	p.Asp266Glu	missense	Exon 6 of 12	ENSP00000365806.3
	GNL1	ENST00000433809.1	TSL:2	c.792C>G	p.Asp264Glu	missense splice_region	Exon 5 of 5	ENSP00000404728.1
	GNL1	ENST00000487166.1	TSL:3	n.-240C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.32	N
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.11
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.059
Sift	Benign	0.82	T
Sift4G	Benign	1.0	T
Polyphen		0.0060	B
Vest4		0.039
MutPred		0.28		Gain of sheet (P = 0.0061)
MVP		0.16
MPC		0.61
ClinPred		0.18	T
GERP RS		2.6
Varity_R		0.039
gMVP		0.48
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs2074505; hg19: chr6-30521137;