6-30547196-C-G

Variant names:

• chr6-30547196-C-G
• rs761401005
• NM_005275.5:c.1357G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005275.5(GNL1):​c.1357G>C​(p.Val453Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V453M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GNL1 NM_005275.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNL1	NM_005275.5	MANE Select	c.1357G>C	p.Val453Leu	missense	Exon 10 of 12	NP_005266.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNL1	ENST00000376621.8	TSL:1 MANE Select	c.1357G>C	p.Val453Leu	missense	Exon 10 of 12	ENSP00000365806.3	P36915-1
	GNL1	ENST00000464231.1	TSL:1	n.545G>C		splice_region non_coding_transcript_exon	Exon 2 of 2
	GNL1	ENST00000958484.1		c.1417G>C	p.Val473Leu	missense	Exon 10 of 12	ENSP00000628543.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460714 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726718

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111466

Other (OTH) AF: 0.0000166 AC: 1 AN: 60368

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Benign	0.35
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.26	N
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.5	N
PhyloP100		1.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.086
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.017	B
Vest4		0.075
MutPred		0.53		Gain of helix (P = 0.132)
MVP		0.13
MPC		0.65
ClinPred		0.26	T
GERP RS		5.0
Varity_R		0.071
gMVP		0.34
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs761401005; hg19: chr6-30514973;