2-27629051-G-C

Variant names:

• chr2-27629051-G-C
• rs3749147
• ENST00000264718.7:c.35G>C

Variant summary

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

The ENST00000264718.7(GPN1):​c.35G>C​(p.Arg12Thr) 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. 15/20 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: 32)
• Consequence: GPN1 ENST00000264718.7 missense
• 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=0.097278565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000264718.7. 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
	GPN1	NM_007266.4	MANE Select	c.-8G>C		5_prime_UTR	Exon 1 of 14	NP_009197.3
	GPN1	NR_026735.2		n.2G>C		non_coding_transcript_exon	Exon 1 of 12
	GPN1	NM_001145047.2		c.8-324G>C		intron	N/A	NP_001138519.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPN1	ENST00000264718.7	TSL:1	c.35G>C	p.Arg12Thr	missense	Exon 1 of 14	ENSP00000264718.3
	GPN1	ENST00000616939.4	TSL:1	c.35G>C	p.Arg12Thr	missense	Exon 1 of 14	ENSP00000484680.1
	GPN1	ENST00000610189.2	TSL:1 MANE Select	c.-8G>C		5_prime_UTR	Exon 1 of 14	ENSP00000476446.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.90
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.74
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.027
Sift	Benign	0.057	T
Sift4G	Benign	0.54	T
Vest4		0.40
MutPred		0.45		Gain of phosphorylation at R12 (P = 0.017)
MVP		0.17
MPC		0.38
ClinPred		0.17	T
GERP RS		1.9
PromoterAI		-0.14	Neutral
gMVP		0.59
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;