NM_001002909.4:c.3451C>T

Variant names:

• chr17-44398626-G-A
• rs746566647
• NM_001002909.4:c.3451C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

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

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.3451C>T	p.Leu1151Phe	missense	Exon 8 of 8	NP_001002909.1	Q9UKJ3-1
	GPATCH8	NM_001304939.2		c.3376C>T	p.Leu1126Phe	missense	Exon 7 of 7	NP_001291868.1
	GPATCH8	NM_001304940.2		c.3217C>T	p.Leu1073Phe	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.3451C>T	p.Leu1151Phe	missense	Exon 8 of 8	ENSP00000467556.1	Q9UKJ3-1
	GPATCH8	ENST00000587228.5	TSL:1	n.*3337C>T		non_coding_transcript_exon	Exon 9 of 9	ENSP00000468719.1	Q9UKJ3-3
	GPATCH8	ENST00000587228.5	TSL:1	n.*3337C>T		3_prime_UTR	Exon 9 of 9	ENSP00000468719.1	Q9UKJ3-3

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152154 Hom.: 0 Cov.: 31

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

GnomAD2 exomes AF: 0.00000515 AC: 1 AN: 194102 AF XY: 0.00000975

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 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

African (AFR) AF: 0.00 AC: 0 AN: 31088

American (AMR) AF: 0.00 AC: 0 AN: 34476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21250

East Asian (EAS) AF: 0.00 AC: 0 AN: 39234

South Asian (SAS) AF: 0.00 AC: 0 AN: 73062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50482

Middle Eastern (MID) AF: 0.000370 AC: 2 AN: 5402

European-Non Finnish (NFE) AF: 0.0000527 AC: 57 AN: 1081000

Other (OTH) AF: 0.00 AC: 0 AN: 57306

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152154 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74322

African (AFR) AF: 0.0000241 AC: 1 AN: 41424

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.00000827 AC: 1

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	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
PhyloP100		3.8
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
Mutation Taster		=35/65	disease causing

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: rs746566647; hg19: chr17-42475994;