17-44399142-C-T

Variant names:

• chr17-44399142-C-T
• rs727502862
• NM_001002909.4:c.2935G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001002909.4(GPATCH8):​c.2935G>A​(p.Ala979Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A979P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GPATCH8 NM_001002909.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.94

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17017263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH8	NM_001002909.4	c.2935G>A	p.Ala979Thr	missense_variant	Exon 8 of 8	ENST00000591680.6	NP_001002909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH8	ENST00000591680.6	c.2935G>A	p.Ala979Thr	missense_variant	Exon 8 of 8	2	NM_001002909.4	ENSP00000467556.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455798 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724668

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: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.55	T
Sift4G	Benign	0.30	T
Polyphen		0.65	P
Vest4		0.39
MutPred		0.20		Gain of phosphorylation at A979 (P = 0.0424);
MVP		0.14
MPC		0.14
ClinPred		0.52	D
GERP RS		5.1
Varity_R		0.12
gMVP		0.27

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

Other links and lift over

dbSNP: rs727502862; hg19: chr17-42476510;