17-44397903-C-T

Variant names:

• chr17-44397903-C-T
• rs200060507
• NM_001002909.4:c.4174G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001002909.4(GPATCH8):​c.4174G>A​(p.Gly1392Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000629 in 1,612,080 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (2 hom.)
• Consequence: GPATCH8 NM_001002909.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.43
• Publications: 5 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.028816849).
• BP6: Variant 17-44397903-C-T is Benign according to our data. Variant chr17-44397903-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 723189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

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.4174G>A	p.Gly1392Ser	missense	Exon 8 of 8	NP_001002909.1	Q9UKJ3-1
	GPATCH8	NM_001304939.2		c.4099G>A	p.Gly1367Ser	missense	Exon 7 of 7	NP_001291868.1
	GPATCH8	NM_001304940.2		c.3940G>A	p.Gly1314Ser	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.4174G>A	p.Gly1392Ser	missense	Exon 8 of 8	ENSP00000467556.1	Q9UKJ3-1
	GPATCH8	ENST00000587228.5	TSL:1	n.*4060G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000468719.1	Q9UKJ3-3
	GPATCH8	ENST00000587228.5	TSL:1	n.*4060G>A		3_prime_UTR	Exon 9 of 9	ENSP00000468719.1	Q9UKJ3-3

Frequencies

GnomAD3 genomes AF: 0.000665 AC: 101 AN: 151976 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000832

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000839

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000726 AC: 182 AN: 250536 AF XY: 0.000761

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00182

Gnomad NFE exome AF: 0.000609

Gnomad OTH exome AF: 0.000817

GnomAD4 exome AF: 0.000625 AC: 913 AN: 1459986 Hom.: 2 Cov.: 32 AF XY: 0.000651 AC XY: 473 AN XY: 726288

African (AFR) AF: 0.000389 AC: 13 AN: 33452

American (AMR) AF: 0.0000895 AC: 4 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00101 AC: 40 AN: 39692

South Asian (SAS) AF: 0.00147 AC: 127 AN: 86224

European-Finnish (FIN) AF: 0.00197 AC: 105 AN: 53250

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.000538 AC: 597 AN: 1110438

Other (OTH) AF: 0.000431 AC: 26 AN: 60336

GnomAD4 genome AF: 0.000664 AC: 101 AN: 152094 Hom.: 0 Cov.: 32 AF XY: 0.000700 AC XY: 52 AN XY: 74322

African (AFR) AF: 0.000265 AC: 11 AN: 41496

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.000833 AC: 4 AN: 4802

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000839 AC: 57 AN: 67964

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000670 Hom.: 1

Bravo AF: 0.000393

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.000865 AC: 105

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.4
PrimateAI	Pathogenic	0.81	D
Sift4G	Uncertain	0.059	T
Polyphen		1.0	D
Vest4		0.56
MVP		0.15
MPC		0.14
ClinPred		0.057	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.66
Mutation Taster		=85/15	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: rs200060507; hg19: chr17-42475271; COSMIC: COSV59194988; COSMIC: COSV59194988;