rs10416265

Variant names:

• chr19-33114394-A-G
• rs10416265
• NM_018025.3:c.2171A>G
• GPATCH1 p.His724Arg

Variant summary

Our verdict is Benign. The variant received -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. 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.

• 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
• Publications: 64 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018025.3. 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
	GPATCH1	NM_018025.3	MANE Select	c.2171A>G	p.His724Arg	missense	Exon 15 of 20	NP_060495.2
	GPATCH1	NR_135270.2		n.2184A>G		non_coding_transcript_exon	Exon 15 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH1	ENST00000170564.7	TSL:1 MANE Select	c.2171A>G	p.His724Arg	missense	Exon 15 of 20	ENSP00000170564.1	Q9BRR8
	GPATCH1	ENST00000939189.1		c.2237A>G	p.His746Arg	missense	Exon 16 of 21	ENSP00000609248.1
	GPATCH1	ENST00000880979.1		c.2171A>G	p.His724Arg	missense	Exon 15 of 19	ENSP00000551038.1

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

GnomAD2 exomes AF: 0.400 AC: 97074 AN: 242558 AF XY: 0.403

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 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

African (AFR) AF: 0.693 AC: 22491 AN: 32468

American (AMR) AF: 0.377 AC: 15526 AN: 41158

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 8701 AN: 25768

East Asian (EAS) AF: 0.839 AC: 33233 AN: 39616

South Asian (SAS) AF: 0.627 AC: 53314 AN: 84988

European-Finnish (FIN) AF: 0.265 AC: 14129 AN: 53220

Middle Eastern (MID) AF: 0.490 AC: 2801 AN: 5720

European-Non Finnish (NFE) AF: 0.256 AC: 282569 AN: 1104150

Other (OTH) AF: 0.364 AC: 21761 AN: 59734

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

African (AFR) AF: 0.669 AC: 27751 AN: 41458

American (AMR) AF: 0.371 AC: 5661 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1205 AN: 3468

East Asian (EAS) AF: 0.833 AC: 4306 AN: 5168

South Asian (SAS) AF: 0.643 AC: 3095 AN: 4816

European-Finnish (FIN) AF: 0.258 AC: 2731 AN: 10584

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17695 AN: 67984

Other (OTH) AF: 0.391 AC: 825 AN: 2110

Alfa AF: 0.320 Hom.: 47692

Bravo AF: 0.437

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 v4.9

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
PhyloP100		-1.7
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.011
Sift	Benign	0.58	T
Sift4G	Benign	0.53	T
Varity_R		0.020
gMVP		0.047
Mutation Taster		=98/2	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10416265;

hg19: chr19-33605300;

COSMIC: COSV50114971;

COSMIC: COSV50114971;