chr1-26900418-C-G

Variant names:

• chr1-26900418-C-G
• NM_022078.3:c.25G>C

Variant summary

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

The NM_022078.3(GPATCH3):​c.25G>C​(p.Glu9Gln) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPATCH3 NM_022078.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18
• Publications: 0 publications found

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]

NUDC (HGNC:8045): (nuclear distribution C, dynein complex regulator) This gene encodes a nuclear distribution protein that plays an essential role in mitosis and cytokinesis. The encoded protein is involved in spindle formation during mitosis and in microtubule organization during cytokinesis. Pseudogenes of this gene are found on chromosome 2. [provided by RefSeq, Feb 2012]

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=0.07694483).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022078.3. 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
	GPATCH3	NM_022078.3	MANE Select	c.25G>C	p.Glu9Gln	missense	Exon 1 of 7	NP_071361.2	Q96I76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH3	ENST00000361720.10	TSL:1 MANE Select	c.25G>C	p.Glu9Gln	missense	Exon 1 of 7	ENSP00000354645.5	Q96I76
	GPATCH3	ENST00000945224.1		c.25G>C	p.Glu9Gln	missense	Exon 1 of 7	ENSP00000615283.1
	NUDC	ENST00000435827.6	TSL:5	c.-101+18C>G		intron	N/A	ENSP00000404020.2	A0A0A0MSU9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.87
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.013
Sift	Benign	0.14	T
Sift4G	Benign	0.27	T
Polyphen		0.10	B
Vest4		0.35
MutPred		0.28		Loss of disorder (P = 0.098)
MVP		0.030
MPC		0.20
ClinPred		0.092	T
GERP RS		3.7
PromoterAI		-0.075	Neutral
Varity_R		0.098
gMVP		0.71
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr1-27226909;