rs147776239

Variant names:

• chr1-26892705-C-G
• NM_022078.3:c.1198G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-26892705-C-G
• chr1-26892705-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022078.3(GPATCH3):​c.1198G>C​(p.Glu400Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. E400K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPATCH3 NM_022078.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058170885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH3	NM_022078.3	c.1198G>C	p.Glu400Gln	missense_variant	Exon 5 of 7	ENST00000361720.10	NP_071361.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH3	ENST00000361720.10	c.1198G>C	p.Glu400Gln	missense_variant	Exon 5 of 7	1	NM_022078.3	ENSP00000354645.5
GPATCH3	ENST00000445019.5	c.145G>C	p.Glu49Gln	missense_variant	Exon 2 of 3	3		ENSP00000398563.1
GPATCH3	ENST00000450844.1	c.52G>C	p.Glu18Gln	missense_variant	Exon 1 of 3	2		ENSP00000399036.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.43
DANN	Benign	0.60
DEOGEN2	Benign	0.015	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.67	N;N
REVEL	Benign	0.022
Sift	Benign	0.44	T;T
Sift4G	Benign	0.54	T;.
Polyphen		0.0010	B;.
Vest4		0.14
MutPred		0.22		Gain of MoRF binding (P = 0.0243);.;
MVP		0.13
MPC		0.15
ClinPred		0.030	T
GERP RS		-3.6
Varity_R		0.027
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr1-27219196;