chr17-44399142-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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 Uncertain significance.

• 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
• Publications: 2 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 0 ACMG points.

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

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.2935G>A	p.Ala979Thr	missense	Exon 8 of 8	NP_001002909.1	Q9UKJ3-1
	GPATCH8	NM_001304939.2		c.2860G>A	p.Ala954Thr	missense	Exon 7 of 7	NP_001291868.1
	GPATCH8	NM_001304940.2		c.2701G>A	p.Ala901Thr	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.2935G>A	p.Ala979Thr	missense	Exon 8 of 8	ENSP00000467556.1	Q9UKJ3-1
	GPATCH8	ENST00000587228.5	TSL:1	n.*2821G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000468719.1	Q9UKJ3-3
	GPATCH8	ENST00000587228.5	TSL:1	n.*2821G>A		3_prime_UTR	Exon 9 of 9	ENSP00000468719.1	Q9UKJ3-3

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

African (AFR) AF: 0.00 AC: 0 AN: 33362

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106704

Other (OTH) AF: 0.00 AC: 0 AN: 60190

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		4.9
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

Other links and lift over

dbSNP: rs727502862; hg19: chr17-42476510;