2-27629051-G-T

Variant names:

• chr2-27629051-G-T
• rs3749147
• NM_007266.4:c.-8G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007266.4(GPN1):​c.-8G>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPN1 NM_007266.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742
• Publications: 0 publications found

Genes affected

GPN1 (HGNC:17030): (GPN-loop GTPase 1) This gene encodes a guanosine triphosphatase enzyme. The encoded protein may play a role in DNA repair and may function in activation of transcription. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

ENSG00000259080 (HGNC:):

CCDC121 (HGNC:25833): (coiled-coil domain containing 121)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11309415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPN1	NM_007266.4	c.-8G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 14	ENST00000610189.2	NP_009197.3
GPN1	NM_007266.4	c.-8G>T		5_prime_UTR_variant	Exon 1 of 14	ENST00000610189.2	NP_009197.3
CCDC121	NM_024584.5	c.-220C>A		upstream_gene_variant		ENST00000324364.4	NP_078860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPN1	ENST00000610189.2	c.-8G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 14	1	NM_007266.4	ENSP00000476446.1
GPN1	ENST00000610189.2	c.-8G>T		5_prime_UTR_variant	Exon 1 of 14	1	NM_007266.4	ENSP00000476446.1
CCDC121	ENST00000324364.4	c.-220C>A		upstream_gene_variant		1	NM_024584.5	ENSP00000339087.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.90
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.38	T;.
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.74
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.19	.;N
REVEL	Benign	0.015
Sift	Uncertain	0.014	.;D
Sift4G	Benign	0.10	T;T
Vest4		0.46
MutPred		0.40		Loss of methylation at R12 (P = 0.0303);Loss of methylation at R12 (P = 0.0303);
MVP		0.21
MPC		0.45
ClinPred		0.66	D
GERP RS		1.9
PromoterAI		-0.065	Neutral
gMVP		0.60
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3749147; hg19: chr2-27851918;