1-26891117-C-G

Variant names:

• chr1-26891117-C-G
• NM_022078.3:c.1471G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022078.3(GPATCH3):​c.1471G>C​(p.Glu491Gln) variant causes a missense change. 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: GPATCH3 NM_022078.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.59

Genes affected

GPATCH3 (HGNC:25720): (G-patch domain containing 3) Predicted to enable nucleic acid binding activity. Involved in negative regulation of RIG-I signaling pathway; negative regulation of type I interferon production; and positive regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26758766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH3	NM_022078.3	c.1471G>C	p.Glu491Gln	missense_variant	Exon 7 of 7	ENST00000361720.10	NP_071361.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH3	ENST00000361720.10	c.1471G>C	p.Glu491Gln	missense_variant	Exon 7 of 7	1	NM_022078.3	ENSP00000354645.5
GPATCH3	ENST00000445019.5	c.181-266G>C		intron_variant	Intron 2 of 2	3		ENSP00000398563.1
GPATCH3	ENST00000450844.1	c.325G>C	p.Glu109Gln	missense_variant	Exon 3 of 3	2		ENSP00000399036.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1471G>C (p.E491Q) alteration is located in exon 7 (coding exon 7) of the GPATCH3 gene. This alteration results from a G to C substitution at nucleotide position 1471, causing the glutamic acid (E) at amino acid position 491 to be replaced by a glutamine (Q). 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	0.19
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.15
Sift	Benign	0.048	D;D
Sift4G	Benign	0.099	T;.
Polyphen		0.80	P;.
Vest4		0.26
MutPred		0.10		Gain of helix (P = 0.062);.;
MVP		0.37
MPC		0.51
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.21
gMVP		0.37

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-27217608;