chr19-33114394-A-G

Position:

• chr19-33114394-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018025.3(GPATCH1):​c.2171A>G​(p.His724Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,598,886 control chromosomes in the GnomAD database, including 103,536 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.42 (16313 hom., cov: 32)
  • Exomes 𝑓: 0.31 (87223 hom.)
• Consequence: GPATCH1 NM_018025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1877081E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPATCH1	NM_018025.3	c.2171A>G	p.His724Arg	missense_variant	15/20	ENST00000170564.7	NP_060495.2
GPATCH1	NR_135270.2	n.2184A>G		non_coding_transcript_exon_variant	15/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPATCH1	ENST00000170564.7	c.2171A>G	p.His724Arg	missense_variant	15/20	1	NM_018025.3	ENSP00000170564	P1
GPATCH1	ENST00000592262.1	n.1107A>G		non_coding_transcript_exon_variant	2/7	2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63563 AN: 151946 Hom.: 16278 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.388

GnomAD3 exomes AF: 0.400 AC: 97074 AN: 242558 Hom.: 24038 AF XY: 0.403 AC XY: 53090 AN XY: 131780

Gnomad AFR exome AF: 0.678

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.344

Gnomad EAS exome AF: 0.847

Gnomad SAS exome AF: 0.635

Gnomad FIN exome AF: 0.266

Gnomad NFE exome AF: 0.264

Gnomad OTH exome AF: 0.356

GnomAD4 exome AF: 0.314 AC: 454525 AN: 1446822 Hom.: 87223 Cov.: 32 AF XY: 0.323 AC XY: 232693 AN XY: 720240

Gnomad4 AFR exome AF: 0.693

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.839

Gnomad4 SAS exome AF: 0.627

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.419 AC: 63659 AN: 152064 Hom.: 16313 Cov.: 32 AF XY: 0.426 AC XY: 31675 AN XY: 74344

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.391

Alfa AF: 0.307 Hom.: 21493

Bravo AF: 0.437

TwinsUK AF: 0.254 AC: 941

ALSPAC AF: 0.254 AC: 977

ESP6500AA AF: 0.672 AC: 2963

ESP6500EA AF: 0.272 AC: 2340

ExAC AF: 0.406 AC: 49243

Asia WGS AF: 0.710 AC: 2463 AN: 3478

EpiCase AF: 0.279

EpiControl AF: 0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0020
DANN	Benign	0.20
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.011
Sift	Benign	0.58	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.016
MPC		0.16
ClinPred		0.0033	T
GERP RS		-8.9
Varity_R		0.020
gMVP		0.047

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

LitVar

Other links and lift over

dbSNP: rs10416265; hg19: chr19-33605300; COSMIC: COSV50114971; COSMIC: COSV50114971;