NM_018025.3:c.80G>A

Variant names:

• chr19-33088140-G-A
• rs745901089
• NM_018025.3:c.80G>A

Variant summary

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

The NM_018025.3(GPATCH1):​c.80G>A​(p.Arg27Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.000017 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GPATCH1 NM_018025.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.43
• Publications: 1 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=0.10013732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH1	NM_018025.3	c.80G>A	p.Arg27Lys	missense_variant	Exon 2 of 20	ENST00000170564.7	NP_060495.2
GPATCH1	XM_006723255.5	c.80G>A	p.Arg27Lys	missense_variant	Exon 2 of 14		XP_006723318.1
GPATCH1	NR_135270.2	n.93G>A		non_coding_transcript_exon_variant	Exon 2 of 21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH1	ENST00000170564.7	c.80G>A	p.Arg27Lys	missense_variant	Exon 2 of 20	1	NM_018025.3	ENSP00000170564.1
GPATCH1	ENST00000592165.1	n.80G>A		non_coding_transcript_exon_variant	Exon 2 of 10	5		ENSP00000467632.1

Frequencies

GnomAD3 genomes AF: 0.0000166 AC: 2 AN: 120500 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000237

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000168

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000655 AC: 11 AN: 167922 AF XY: 0.0000862

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000593

Gnomad NFE exome AF: 0.0000238

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000430 AC: 47 AN: 1093842 Hom.: 0 Cov.: 23 AF XY: 0.0000441 AC XY: 24 AN XY: 544308

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24580

American (AMR) AF: 0.0000417 AC: 1 AN: 24000

Ashkenazi Jewish (ASJ) AF: 0.000106 AC: 2 AN: 18930

East Asian (EAS) AF: 0.0000605 AC: 2 AN: 33032

South Asian (SAS) AF: 0.0000362 AC: 2 AN: 55228

European-Finnish (FIN) AF: 0.000544 AC: 21 AN: 38586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3610

European-Non Finnish (NFE) AF: 0.0000212 AC: 18 AN: 850756

Other (OTH) AF: 0.0000222 AC: 1 AN: 45120

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000166 AC: 2 AN: 120562 Hom.: 0 Cov.: 27 AF XY: 0.0000175 AC XY: 1 AN XY: 57286

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31636

American (AMR) AF: 0.00 AC: 0 AN: 11036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3080

East Asian (EAS) AF: 0.000237 AC: 1 AN: 4212

South Asian (SAS) AF: 0.00 AC: 0 AN: 3732

European-Finnish (FIN) AF: 0.000168 AC: 1 AN: 5950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58274

Other (OTH) AF: 0.00 AC: 0 AN: 1606

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.80G>A (p.R27K) alteration is located in exon 2 (coding exon 2) of the GPATCH1 gene. This alteration results from a G to A substitution at nucleotide position 80, causing the arginine (R) at amino acid position 27 to be replaced by a lysine (K). 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	0.098
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Benign	0.69
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-0.072
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.12
Sift	Benign	0.51	T
Sift4G	Benign	1.0	T
Polyphen		0.26	B
Vest4		0.34
MVP		0.44
MPC		0.13
ClinPred		0.15	T
GERP RS		5.3
Varity_R		0.14
gMVP		0.26
Mutation Taster		=91/9	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: rs745901089; hg19: chr19-33579046;