Variant rs2287679 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Variant links:

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]

GPATCH1 links:

GPATCH1 (HGNC:):

GPATCH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
GPATCH1	NM_018025.3 linkuse as main transcript	c.1427T>C	p.Leu476Pro	missense_variant	11/20	ENST00000170564.7	NP_060495.2	Q9BRR8
GPATCH1	XM_006723255.5 linkuse as main transcript	c.1427T>C	p.Leu476Pro	missense_variant	11/14		XP_006723318.1
GPATCH1	NR_135270.2 linkuse as main transcript	n.1440T>C		non_coding_transcript_exon_variant	11/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GPATCH1	ENST00000170564.7 linkuse as main transcript	c.1427T>C	p.Leu476Pro	missense_variant	11/20	1	NM_018025.3	ENSP00000170564.1	Q9BRR8
GPATCH1	ENST00000592165.1 linkuse as main transcript	n.*883T>C		non_coding_transcript_exon_variant	10/10	5		ENSP00000467632.1	K7EQ19
GPATCH1	ENST00000592165.1 linkuse as main transcript	n.*883T>C		3_prime_UTR_variant	10/10	5		ENSP00000467632.1	K7EQ19
GPATCH1	ENST00000590062.1 linkuse as main transcript	n.-19T>C		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62983

AN:

151984

Hom.:

16496

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.307

AC XY:

223339

AN XY:

727126

show subpopulations

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.:

AF XY:

0.418

AC XY:

31060

AN XY:

74348

show subpopulations

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

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.015

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0000018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.10

REVEL

Benign

0.11

Sift

Benign

0.36

Sift4G

Benign

0.25

Polyphen

0.0

Vest4

0.016

MPC

0.21

ClinPred

0.0011

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over