chr19-33081245-G-C

Variant names:

• chr19-33081245-G-C
• rs766935903
• NM_018025.3:c.52G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018025.3(GPATCH1):​c.52G>C​(p.Gly18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000277 in 1,551,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: GPATCH1 NM_018025.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47
• Publications: 0 publications found

Genes affected

GPATCH1 (HGNC:24658): (G-patch domain containing 1) Predicted to enable RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Part of catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13706705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH1	NM_018025.3	c.52G>C	p.Gly18Arg	missense_variant	Exon 1 of 20	ENST00000170564.7	NP_060495.2
GPATCH1	XM_006723255.5	c.52G>C	p.Gly18Arg	missense_variant	Exon 1 of 14		XP_006723318.1
GPATCH1	NR_135270.2	n.65G>C		non_coding_transcript_exon_variant	Exon 1 of 21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH1	ENST00000170564.7	c.52G>C	p.Gly18Arg	missense_variant	Exon 1 of 20	1	NM_018025.3	ENSP00000170564.1
GPATCH1	ENST00000592165.1	n.52G>C		non_coding_transcript_exon_variant	Exon 1 of 10	5		ENSP00000467632.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000959 AC: 15 AN: 156478 AF XY: 0.0000971

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000323

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000227

GnomAD4 exome AF: 0.0000250 AC: 35 AN: 1399350 Hom.: 0 Cov.: 31 AF XY: 0.0000290 AC XY: 20 AN XY: 690208

African (AFR) AF: 0.0000316 AC: 1 AN: 31628

American (AMR) AF: 0.000364 AC: 13 AN: 35710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35772

South Asian (SAS) AF: 0.000227 AC: 18 AN: 79226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078962

Other (OTH) AF: 0.0000517 AC: 3 AN: 57982

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2 AN XY: 74506

African (AFR) AF: 0.00 AC: 0 AN: 41596

American (AMR) AF: 0.000458 AC: 7 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000126 AC: 1

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.52G>C (p.G18R) alteration is located in exon 1 (coding exon 1) of the GPATCH1 gene. This alteration results from a G to C substitution at nucleotide position 52, causing the glycine (G) at amino acid position 18 to be replaced by an arginine (R). 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	0.34
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.087
FATHMM_MKL	Benign	0.48	N
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.11
Sift	Benign	0.056	T
Sift4G	Uncertain	0.037	D
Polyphen		0.92	P
Vest4		0.47
MutPred		0.28		Gain of solvent accessibility (P = 0.0471);
MVP		0.34
MPC		0.20
ClinPred		0.13	T
GERP RS		3.3
PromoterAI		-0.028	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.11
gMVP		0.55
Mutation Taster		=93/7	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

dbSNP: rs766935903; hg19: chr19-33572151;