17-44398626-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001002909.4(GPATCH8):​c.3451C>T​(p.Leu1151Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000414 in 1,545,454 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000042 ( 1 hom. )

Consequence

GPATCH8
NM_001002909.4 missense

Scores

7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.42149386).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPATCH8NM_001002909.4 linkc.3451C>T p.Leu1151Phe 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
GPATCH8ENST00000591680.6 linkc.3451C>T p.Leu1151Phe missense_variant Exon 8 of 8 2 NM_001002909.4 ENSP00000467556.1 Q9UKJ3-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152154
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000515
AC:
1
AN:
194102
Hom.:
0
AF XY:
0.00000975
AC XY:
1
AN XY:
102520
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000108
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000423
AC:
59
AN:
1393300
Hom.:
1
Cov.:
34
AF XY:
0.0000423
AC XY:
29
AN XY:
686186
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000527
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152154
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ExAC
AF:
0.00000827
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3451C>T (p.L1151F) alteration is located in exon 8 (coding exon 8) of the GPATCH8 gene. This alteration results from a C to T substitution at nucleotide position 3451, causing the leucine (L) at amino acid position 1151 to be replaced by a phenylalanine (F). 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
Uncertain
0.40
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.077
T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.42
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N
PrimateAI
Uncertain
0.62
T
Sift4G
Benign
0.23
T
Polyphen
1.0
D
Vest4
0.57
MutPred
0.14
Loss of MoRF binding (P = 0.1315);
MVP
0.14
MPC
0.15
ClinPred
0.41
T
GERP RS
5.0
Varity_R
0.26
gMVP
0.40

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.

Other links and lift over

dbSNP: rs746566647; hg19: chr17-42475994; API