chr19-33090831-C-A

Position:

• chr19-33090831-C-A

Variant summary

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

The NM_018025.3(GPATCH1):​c.260C>A​(p.Ser87Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: GPATCH1 NM_018025.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02

Genes affected

GPATCH1 (HGNC:24658): (G-patch domain containing 1) Predicted to enable RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Part of catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

GPATCH1 (HGNC:):

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=0.19553733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPATCH1	NM_018025.3	c.260C>A	p.Ser87Tyr	missense_variant	3/20	ENST00000170564.7	NP_060495.2
GPATCH1	XM_006723255.5	c.260C>A	p.Ser87Tyr	missense_variant	3/14		XP_006723318.1
GPATCH1	NR_135270.2	n.273C>A		non_coding_transcript_exon_variant	3/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPATCH1	ENST00000170564.7	c.260C>A	p.Ser87Tyr	missense_variant	3/20	1	NM_018025.3	ENSP00000170564.1
GPATCH1	ENST00000592165.1	n.260C>A		non_coding_transcript_exon_variant	3/10	5		ENSP00000467632.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461162 Hom.: 0 Cov.: 29 AF XY: 0.00000825 AC XY: 6 AN XY: 726958

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: 0.00000810

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000624 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.260C>A (p.S87Y) alteration is located in exon 3 (coding exon 3) of the GPATCH1 gene. This alteration results from a C to A substitution at nucleotide position 260, causing the serine (S) at amino acid position 87 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.038	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.096
Sift	Benign	0.061	T
Sift4G	Benign	0.19	T
Polyphen		0.65	P
Vest4		0.24
MutPred		0.51		Loss of disorder (P = 0.0044);
MVP		0.29
MPC		0.40
ClinPred		0.86	D
GERP RS		6.0
Varity_R		0.18
gMVP		0.28

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: rs1972586266; hg19: chr19-33581737;