rs140497485

Variant names:

• chr17-44398604-T-G
• rs140497485
• NM_001002909.4:c.3473A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-44398604-T-G
• chr17-44398604-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 13/20 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.325
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010875344).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002909.4. 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
	GPATCH8	NM_001002909.4	MANE Select	c.3473A>C	p.Asn1158Thr	missense	Exon 8 of 8	NP_001002909.1	Q9UKJ3-1
	GPATCH8	NM_001304939.2		c.3398A>C	p.Asn1133Thr	missense	Exon 7 of 7	NP_001291868.1
	GPATCH8	NM_001304940.2		c.3239A>C	p.Asn1080Thr	missense	Exon 10 of 10	NP_001291869.1	Q9UKJ3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH8	ENST00000591680.6	TSL:2 MANE Select	c.3473A>C	p.Asn1158Thr	missense	Exon 8 of 8	ENSP00000467556.1	Q9UKJ3-1
	GPATCH8	ENST00000587228.5	TSL:1	n.*3359A>C		non_coding_transcript_exon	Exon 9 of 9	ENSP00000468719.1	Q9UKJ3-3
	GPATCH8	ENST00000587228.5	TSL:1	n.*3359A>C		3_prime_UTR	Exon 9 of 9	ENSP00000468719.1	Q9UKJ3-3

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152148 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000134 AC: 26 AN: 193736 AF XY: 0.000146

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 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.: 1 Cov.: 34 AF XY: 0.0000826 AC XY: 57 AN XY: 689700

African (AFR) AF: 0.0000642 AC: 2 AN: 31136

American (AMR) AF: 0.00 AC: 0 AN: 34386

Ashkenazi Jewish (ASJ) AF: 0.000606 AC: 13 AN: 21456

East Asian (EAS) AF: 0.00 AC: 0 AN: 39334

South Asian (SAS) AF: 0.0000543 AC: 4 AN: 73632

European-Finnish (FIN) AF: 0.0000197 AC: 1 AN: 50658

Middle Eastern (MID) AF: 0.00110 AC: 6 AN: 5430

European-Non Finnish (NFE) AF: 0.0000729 AC: 79 AN: 1084366

Other (OTH) AF: 0.000174 AC: 10 AN: 57530

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68006

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000113

ExAC AF: 0.000116 AC: 14

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.63	N
PhyloP100		-0.33
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.22	T
Polyphen		0.10	B
Vest4		0.14
MutPred		0.17		Gain of phosphorylation at N1158 (P = 0.0055)
MVP		0.043
MPC		0.14
ClinPred		0.012	T
GERP RS		1.5
Varity_R		0.032
gMVP		0.043
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs140497485; hg19: chr17-42475972;