Genetic Variant GPATCH8:p.Asn1158Thr (chr17-44398604-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001002909.4(GPATCH8):c.3473A>C(p.Asn1158Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000826 in 1,550,076 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 1 hom. )

Consequence

GPATCH8
NM_001002909.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.325

Variant links:

Genes affected

GPATCH8 (HGNC:29066): (G-patch domain containing 8) The protein encoded by this gene contains an RNA-processing domain, a zinc finger domain, a lysine-rich region and a serine-rich region. A mutation in the serine-rich region of the protein is thought to be associated with hyperuricemia (PMID: 21594610). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]

GPATCH8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010875344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH8	NM_001002909.4 link	c.3473A>C	p.Asn1158Thr	missense_variant	Exon 8 of 8	ENST00000591680.6	NP_001002909.1	Q9UKJ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH8	ENST00000591680.6 link	c.3473A>C	p.Asn1158Thr	missense_variant	Exon 8 of 8	2	NM_001002909.4	ENSP00000467556.1		Q9UKJ3-1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000134

AC:

AN:

193736

Hom.:

AF XY:

0.000146

AC XY:

AN XY:

102644

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000586

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000162

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000823

AC:

115

AN:

1397928

Hom.:

Cov.:

AF XY:

0.0000826

AC XY:

AN XY:

689700

show subpopulations

Gnomad4 AFR exome

AF:

0.0000642

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000606

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000543

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.0000729

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.000113

ExAC

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3473A>C (p.N1158T) alteration is located in exon 8 (coding exon 8) of the GPATCH8 gene. This alteration results from a A to C substitution at nucleotide position 3473, causing the asparagine (N) at amino acid position 1158 to be replaced by a threonine (T). 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

0.064

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.024

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.47

M_CAP

Benign

0.0046

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.63

PrimateAI

Benign

0.38

Sift4G

Benign

0.22

Polyphen

0.10

Vest4

0.14

MutPred

0.17

Gain of phosphorylation at N1158 (P = 0.0055);

MVP

0.043

MPC

0.14

ClinPred

0.012

GERP RS

1.5

Varity_R

0.032

gMVP

0.043

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over