rs2287679

Positions:

• chr19-33109858-T-C
• chr19-33109858-T-G

Variant summary

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

The NM_018025.3(GPATCH1):​c.1427T>C​(p.Leu476Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,613,746 control chromosomes in the GnomAD database, including 92,389 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 0.41 (16536 hom., cov: 32)
  • Exomes 𝑓: 0.30 (75853 hom.)
• Consequence: GPATCH1 NM_018025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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=1.7734677E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPATCH1	NM_018025.3	c.1427T>C	p.Leu476Pro	missense_variant	11/20	ENST00000170564.7
GPATCH1	XM_006723255.5	c.1427T>C	p.Leu476Pro	missense_variant	11/14
GPATCH1	NR_135270.2	n.1440T>C		non_coding_transcript_exon_variant	11/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPATCH1	ENST00000170564.7	c.1427T>C	p.Leu476Pro	missense_variant	11/20	1	NM_018025.3	P1
GPATCH1	ENST00000592165.1	c.*883T>C		3_prime_UTR_variant, NMD_transcript_variant	10/10	5
GPATCH1	ENST00000590062.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62983 AN: 151984 Hom.: 16496 Cov.: 32

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.377

GnomAD3 exomes AF: 0.358 AC: 89655 AN: 250630 Hom.: 19442 AF XY: 0.364 AC XY: 49332 AN XY: 135634

Gnomad AFR exome AF: 0.740

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.317

Gnomad EAS exome AF: 0.514

Gnomad SAS exome AF: 0.609

Gnomad FIN exome AF: 0.250

Gnomad NFE exome AF: 0.259

Gnomad OTH exome AF: 0.324

GnomAD4 exome AF: 0.298 AC: 436233 AN: 1461644 Hom.: 75853 Cov.: 35 AF XY: 0.307 AC XY: 223339 AN XY: 727126

Gnomad4 AFR exome AF: 0.751

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.314

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.604

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome AF: 0.415 AC: 63077 AN: 152102 Hom.: 16536 Cov.: 32 AF XY: 0.418 AC XY: 31060 AN XY: 74348

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.380

Alfa AF: 0.296 Hom.: 16444

Bravo AF: 0.432

TwinsUK AF: 0.249 AC: 923

ALSPAC AF: 0.250 AC: 963

ESP6500AA AF: 0.727 AC: 3203

ESP6500EA AF: 0.267 AC: 2297

ExAC AF: 0.370 AC: 44902

Asia WGS AF: 0.588 AC: 2041 AN: 3478

EpiCase AF: 0.274

EpiControl AF: 0.271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.041
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.61
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0000018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.11
Sift	Benign	0.36	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.016
MPC		0.21
ClinPred		0.0011	T
GERP RS		5.7
Varity_R		0.051
gMVP		0.25

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: rs2287679; hg19: chr19-33600764; COSMIC: COSV50111027; COSMIC: COSV50111027;